REVIEWS

Asymmetric cell division in land

plants and algae: the driving force
for differentiation
Ive De Smet*‡§ and Tom Beeckman‡§
Abstract | Asymmetric cell division generates two cells with different fates and has an
important role in plant development. It produces distinct cell types and new organs, and
maintains stem cell niches. To handle the constraints of having immobile cells, plants
possess numerous unique features to obtain asymmetry, such as specific regulators of
intrinsic polarity. Although several components have not yet been identified, new findings,
together with knowledge from different developmental systems, now allow us to take an
important step towards a mechanistic overview of asymmetric cell division in plants and
algae. Strikingly, several key regulators are used for different developmental processes,
and common mechanisms can be recognized.

Stem cell niche

The environment that provides
signals and physical support to
maintain stem cells.
Preprophase band
A modification of the plant
cortical cytoskeleton in cells
preparing to divide, consisting of
a ring of actin and microtubules
that transiently marks the plane
of cell division.
*Plant and Crop Sciences
Division, School of
Biosciences, University of
Nottingham, Loughborough
LE12 5RD, UK.
‡Department of Plant Systems
Biology, VIB, Technologiepark
927, 9052 Gent, Belgium.
§Department of Plant
Biotechnology and Genetics,
Ghent University,
Technologiepark 927, 9052
Gent, Belgium. e-mails:
Ive.De_Smet@
nottingham.ac.uk;
tobee@psb.vib-ugent.be
doi:10.1038/nrm3064
Corrected online 23 March
2011
Asymmetric cell division is essential in many organisms
to generate cell diversity and tissue patterns and to
maintain pools of stem cells1–4. In plants and multi-cellular
algae, asymmetric cell division is of particular importance,
as their post-embryonic growth is based on de novo
formation of cell types, tissues and even entirely new
organs (BOX 1). Because of the immobility of plant and
algae cells, which are ‘caged’ within the cell wall, correct
development of the multicellular body relies on strict
coordination of asymmetric cell divisions in space and
time. Such divisions can result in two daughter cells with
different sizes. More importantly, at the molecu-lar level
this is achieved by the differential inheritance of proteins
that establish polarity and that are respon-sible, together
with other cellular components, for the differentiation of
distinct cell types (FIG. 1a) . Besides this, different cell fates
of initially equivalent daughter cells can be achieved
through intrinsic factors (FIG. 1b) or extrinsic factors (for
example, the surrounding cells that comprise the stem cell
niche) that convey positional information (FIG. 1c). It is
becoming clear that every asymmetric cell division
depends on both intrinsic and extrinsic factors
simultaneously, and this explains why the mechanisms
involved can rarely be distinguished.
Throughout the whole process of asymmetric cell
division in plants and algae, many steps, which are not
necessarily all present in every asymmetric cell division
process, can be identified (FIG. 1a–c). First is the
specification of a subset of cells that will undergo
asymmetric cell division5,6. Second, numerous cellular
events take place
(not necessarily in the following order): polar localiza-
tion of proteins7; establishment of gradients8–10; correct
positioning of the nucleus11; polar accumulation of
cytoplasm12; and formation of the preprophase band,
spindle and cell plate13. Third, asymmetrically
distributed and expressed cell fate determinants control
the identity and future development of both daughter
cells into a differentiated tissue or organ1.
In the past, the study of asymmetric cell division in
plants was fragmentary and often confined to one single
developmental process during the life cycle of plants and
alge, which did not allow the recognition of common
molecular mechanisms. Recently, key players have been
identified in several processes, urging for a new overview
of the key steps and molecular players. In this Review, we
search for potential common themes driving cell
differentiation and attempt to produce a global image of
asymmetric cell division in plants and algae by discussing
available data for the events that accompany this process.
Occurrence of asymmetric cell divisions
There are several representative examples of asymmetric
divisions in which physical asymmetry is coupled to the
generation of new cell fates throughout plant development
(BOXES 1,2; FIG. 2).
One such example is the formation of the male germ
line in flowering plants, during which haploid microspores
divide asymmetrically to form a large vegetative cell and a
small generative cell that subsequently divides
symmetrically to produce two sperm cells14 (BOX 1; FIG. 2a).

NATURE REVIEWS | MOLECULAR CELL BIOLOGY VOLUME 12 | MARCH 2011 | 177

© 2011 Macmillan Publishers Limited. All rights reserved
REVIEWS

hypocotyl, respectively. The basal daughter cell produces

Box 1 | Basic steps of plant development
the suspensor, a file of six to nine cells, the uppermost of
C D which forms the hypophysis. During early embryogenesis,
%QV[NGFQP the root meristem is determined by asymmetric division
8GIGVCVKXGPWENGWU
of the hypophysis, which generates a small lens-shaped
daughter cell that will become the organizing centre of the
%QV[NGFQP root apical meristem16–18 (BOX 1; FIG. 2c). At the dermatogen
5#/ stage during plant embryogenesis, the protoderm and the
inner tissues become specified through asymmetric divisions
5RGTOEGNNPWENGK
Tangential divisions of the eight cells of the octant
stage embryo produce two distinct cell types, each with
specific marker gene expression17,18 (FIG. 2c).
H #TCDKFQRUKUVJCNKCPC After germination, well-defined examples of asym-
4#/
)WCTFEGNN metric divisions can be observed during lateral root
initiation19 and stomata development20. Lateral root initia-
E tion in A. thaliana requires several rounds of asymmetric,
anticlinal cell divisions that give rise to the central core of
.CVGTCNTQQV small pericycle cells, which express different markers to
2CXGOGPVEGNN larger surrounding cells19. A series of subsequent cell divisions,
<GCOC[U 5WDUKFKCT[EGNN
which are largely invariant11,19,21, give rise to a lateral
/CKPTQQV
root primordium with an identical layout to the main root
)WCTFEGNN apical meristem (BOX 1; FIG. 2d). In leaves of dicotyledons
G F and monocotyledons, stomata are the final product of
a series of asymmetric cell divisions in the protoderm20
3WKGUEGPV (BOX 1; FIG. 2e,f). In the dicotyledon A. thaliana, the stomatal
2CXGOGPVEGNN EGPVTG lineage is initiated in one protodermal cell, the
:[NGO meristemoid mother cell, which divides asymmetrically
2GTKE[ENG
2JNQGO to form the meristemoid (FIG. 2e). This then divides
'PFQFGTOKU asymmetrically one to three more times before one of the small
%QTVGZ daughter cells differentiates into a guard mother cell,
'RKFGTOKU
which in turn divides symmetrically to form stomatal
In plants, the male gametophyte or pollen (see the figure, part a) is produced within guard cells (BOX 1). In monocotyledonous grasses, such
the anthers of the flower, where reproductive cells give rise to the microspores and as Zea mays (maize), files of cells divide asymmetrically
non-reproductive cells form discrete anther tissue layers. In the microspore, the upon polarization, and one daughter cell differentiates
displaced nucleus undergoes pollen mitosis, resulting in the formation of two unequal into a guard mother cell. Subsequently, neighbouring cells
cells, a large vegetative cell and a small generative cell. The generative cell undergoes a in adjacent files of cells, known as subsidiary mother cells,
second mitosis to form two sperm cells. After fertilization, plants, like animals, develop
divide asymmetrically towards the guard mother cell to
an embryo (see the figure, part b) through an invariant series of cell divisions. During
their life cycle, plants strongly rely on post-embryonic development through the produce subsidiary cells (BOX 1; FIG. 2f).
continuous activity of meristems, which are a group of cells consisting of pluripotent However, cell divisions generating daughter cells with
stem cells and highly proliferating daughter cells. To build their primary adult body, different fates are not always spatially asymmetric, and
the shoot apical meristem (SAM) and the root apical meristem (RAM) produce the shoot symmetrically divided cells can adopt different fates based
and root, respectively, and branching of the root is accomplished by de novo-formed on intrinsic factors, external cues or positional information.
lateral root meristems (see the figure, part c). The root meristem contains a stem This is most apparent in stem cells in root meristems,
cell niche that is maintained through an organizing centre, known as the quiescent where cell-to-cell contact with neighbouring cells
centre (see the figure, part d), and that continuously gives rise to new cells, resulting in is crucial in maintaining stem cell pools. In this case, the
concentric layers of root tissue. These are the epidermis, cortex, endodermis, pericycle daughter cell that is in contact with the organizing centre
and vasculature — including xylem and phloem (see the figure, part e). Stomata
keeps its stem cell identity after division. The root stem
development occurs in the epidermis. In Arabidopsis thaliana, large pavement cells
and guard cells can be recognized, and in the Zea mays epidermis, files of pavement cell divisions seem to result in daughter cells of equal size,
cells alternating with two guard cells flanked by subsidiary cells are visible (see the which in some cases can temporarily have similar molecular
figure, part f). Image in part a is reproduced from REF. 123. Image of Zea mays in composition (that is, they show some similarity in transcription
part f is courtesy of L. Smith, University of California, San Diego, USA. factor activity)22 and depend strongly on external
positional control to maintain stem cell identity (BOX 1;
FIG. 2g). Similarly, vascular tissue is established through
Other well-studied cases are the first zygotic division a series of asymmetric cell divisions in the procambium,
in fucoid algae15 (FIG. 2b) and in plants16 (FIG. 2c), which during which one daughter cell differentiates into a vascular
defines apical and basal cell lineages. In brown algae, such cell and the other maintains its stem cell identity23–25.
Microspore as Fucus spp., the apical cell gives rise to thallic tissues and The subsequent differentiation of xylem cell types is
A developing pollen grain
the basal cell to rhizoid tissues. In Arabidopsis thaliana, the determined through bidirectional positional signalling,
(male gametophyte) at the
uninucleate stage within
apical daughter cell produces two tiers of four cells each, specifically through a crosstalk between the GRAS (GAI,
the microsporangia of the which contribute to the apical and central regions of the RGA and SCR) transcription factor SHORT ROOT (SHR)
stamen in seed plants. embryo; these give rise to the shoot apical meristem and and the microRNAs miR165 and miR166 (REF. 26).

178 | MARCH 2011 | VOLUME 12 www.nature.com/reviews/molcellbio

© 2011 Macmillan Publishers Limited. All rights reserved
 REVIEWS

C 'ZVGTPCNUKIPCN All of these developmental steps in the anther depend

! ! highly on positional information, and several receptor-
2QNCTRTQVGKPU 2TGRTQRJCUG like kinases and putative ligands, next to specific
DCPF
transcription factors, were proposed to be involved in
%[VQRNCUO this process28–30.
In the following sections, we summarize and illustrate
0WENGWU the sequence of events and list the molecular players
that accompany asymmetric division, referring, when
necessary, to excellent recent reviews for additional
information.
%GNNURGEKȮECVKQP 2QNCTRTQVGKP 2QUKVKQPKPIQHPWENGWU &KUVKPEVEGNN
NQECNK\CVKQP E[VQRNCUOFGVGTOKPCPVU KFGPVKVKGU Towards asymmetric cell division
ITCFKGPV CPFRTGRTQRJCUGDCPF Asymmetric cell division is preceded by steps that are
GUVCDNKUJOGPV! HQTOCVKQP
crucial to lay down correct cell identities. In general, the
D E processes involved are the following: specification of cells
'ZVGTPCNUKIPCN
destined for asymmetric division; establishment of cell
0KEJG 0KEJG 0KEJG polarity and polar localization of proteins; positioning
of the nucleus and cytoplasm; and positioning of the cell
! ! !
plants and algae. Schematic representation of frequently0CVWTG4GXKGYUoccurring/QNGEWNCTkeyaspects%GNN$KQNQI[ plate. However, it is not always clear what the precise
is bas ed on intercellular trans fer of t rans cription facto rs

5VGO
EGNN
order of these events is, and it is possible that several steps
occur in parallel or at least overlap.

&CWIJVGT Specification of cells destined for asymmetric division.

EGNN Within a complex framework of immobile cells, instructions
to steer asymmetric division require tightly regulated
+PVTKPUKEHCEVQTU
cell-to-cell communication. In several cases, plants
FGVGTOKPGEGNNHCVG
Figure 1 | Main mechanisms for establishment of asymmetric cell identities in
use a non-cell-autonomous system to specify cells, which

during asymmetric cell division that give rise to unequally sized daughter cells (a) and is less common in animals31,32. During stomata
and equally sized daughter cells (b,c). a | Indicated steps are often required during development, for example, restricting overall symplastic
asymmetric cell division, except for the gradient (white to blue), for which there is only movement of identity factors such as transcription factors
some evidence of establishment in algae. After a cell has been specified for asymmetric (for instance through callose blocks) is an important
cell division, a speculated external signal is thought to establish distinct polar domains. mechanism for regulating cell specification of the plant
This is followed by polar localization of proteins, establishment of gradients, positioning epidermis33.
of the nucleus and cytoplasm, formation of the preprophase band and asymmetric During root development, TARGET OF
distribution of cell fate determinants. These events give rise to a small and a large MONOPTEROS 7 (TMO7)5 and SHR34 are two examples
daughter cell. b | Cell fate can be determined through intrinsic factors in equally
of transcription factors (belonging to the basic helix–
sized daughter cells. c | Cell fate can be determined in equally sized daughter cells in
the stem cell niche. This is thought to be mediated, in part, by a protein that localizes loop–helix (bHLH) family and GRAS family, respectively)
in a polar manner and that interprets an external signal defining asymmetric cell division. that move from adjacent cells into the cell that
will undergo an asymmetric division. For example, SHR-
dependent signalling controls the periclinal division of
the stem cell daughter cell and endodermis specification.
In addition, but less established as a model, the To achieve this, SHR moves into the common
Thallic tissue periclinal divisions of the inner core of small pericycle cells stem cell that gives rise to the cortex and endodermis
The body of an alga (thallus).
during lateral root initiation also result in morphologically and into the daughter cells that will become the
Rhizoid tissue similar daughter cells with different identities. Lineage endodermis to establish two of the concentric tissue layers
A branching, filamentous, analysis has shown that these cells contribute to different that make up the radial pattern of the root, namely the
root-like extension by parts of the root primordium21. As such, during the initial cortex and endodermis36 (BOX 1; FIG. 2g). Another example
which algae can attach to
steps of lateral root formation, both morphologically is the specification of the hypophysis during embryo
a substrate and absorb
water and nutrients.
distinguishable and indistinguishable asymmetric cell development, which requires the action of TMO7.
divisions take place (FIG. 2d), rendering these early events Specifically, the auxin response factor MONOPTEROS
Suspensor an ideal model system to study differences between these (MP; also known as ARF5) activates an auxin response
A terminally differentiated two types of asymmetric cell division. in the cells just above the hypophysis, which activates
embryonic cell file that
connects the embryo to
At the reproductive stage in A. thaliana, development the transcription of TMO7, allowing it to move into the
surrounding tissues during of the anther involves asymmetric cell division of the hypophysis5,6 (FIG. 3a).
early seed development. archesporial cell, giving rise to equally sized cells with The auxin response in a neighbouring cell also has
different cell fates, namely primary parietal and primary a role in lateral root initiation, during which lateral root
Hypophysis
sporogenous cells. Further morphologically symmetric founder cells are primed or specified shortly after leaving
The uppermost cell of the
but functionally asymmetric cell divisions of these
basal lineage, called the
daughter the meristem11,37. This requires an auxin response
suspensor, which will give cells result in equally sized cells that are involved in in adjacent protoxylem cells that is involved in regular
rise to the root meristem. the establishment of proper cell identity in the anther 27,28. lateral root organ spacing37, suggesting the existence of

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© 2011 Macmillan Publishers Limited. All rights reserved
REVIEWS
Box 2 | Alternative model systems for asymmetric cell divisions
For stationary plant cells, lineage and fate of single cells in developing or mature tissues
can be followed without disrupting the biology of the event being investigated, an approach
that is possible, but more challenging, in animals142. However, asymmetrically dividing plant
cells are often embedded deep in maternal tissue (in the zygote) or surrounded by various
other cells (in lateral root initiation, the root apical meristem or stomata), making imaging
hard and/or exogenous application of drugs rarely specific to the cell of interest.
Fortunately, in Fucus spp., the newly fertilized zygote is free of surrounding tissue, and both
initial and subsequent cell divisions are similar to those that occur in Arabidopsis thaliana
zygotes15. Therefore, despite being phylogenetically distant to plants, fucoid algae are a
useful alternative for cell biological studies. However, the absence of genetic tools limits the
functional characterization of molecular players. For example, although auxin seems to
have a significant effect on the polarity of zygotes in brown algae143,144, some of the key
auxin response mediators are not present in various green and brown algae 144–146.
Nevertheless, it is possible that the ones present, such as AUXIN-BINDING PROTEIN 1
(ABP1) and the putative dual-specificity protein phosphatase INDOLE-3-BUTYRIC ACID
RESPONSE 5, might be sufficient to interpret auxin-mediated cues144–146. Examining more
genome data and using new transformation protocols might help to address the function of
these proteins in algae and the differences with land plants.
The germinating single-celled spores of the ferns Ceratopteris richardii and Onoclea
sensibilis can also be used as a model to study nuclear migration, as they display
asymmetric division, generating one cell that gives rise to the primary rhizoid and one
that gives rise to the prothallus57,58. Furthermore, the moss Physcomitrella patens
shows asymmetric and self-replacing divisions from the tetrahedral initial, generating
leaf initials that divide asymmetrically to produce daughter cells with restricted fate 68.
It can therefore also be used to identify key players in division-plane determination147.
a mobile factor moving from the protoxylem cells to
the founder cells (FIG. 3b). Several transcription factors
were recently shown to be implicated in this
Dermatogen stage
The embryonic stage during process11,38, in addition to the accumulation of Ca2+ in
which tangential cell divisions lateral root founder cells, which may play a part in
occur, creating tissue layers their specifica-tion39. However, a role for mobile
following the octant stage. transcription factors has not been shown.
Cells can also be specified before asymmetric divi-
Protoderm
The outer layer that will sion, through cell-to-cell communication mediated by
become the epidermis. peptide hormones and associated receptor-like
kinases29. For example, during stomata development,
Stomata
A structure in the epidermis of
entry into the stomatal lineage depends on cell-to- cell
aerial organs that balances gas signalling components, including various putative
exchange and water loss. ligands (such as STOMAGEN), receptor-like kinases
(such as the ERECTA family) and mitogen-activated
Anticlinal cell division
protein kinase (MAPK) cascades that affect
A division at a right angle
to the surface of an organ phosphorylation of trans-cription factors (such as
or plant part. SPEECHLESS), orient asym-metric cell divisions and
prevent overproduction and clustering of stomata20,40–44.
Pericycle
The outermost tissue of the stele
Cell polarity and polar localization of proteins. In cells
(that is, the central column of
vascular and supporting tissues), that are correctly specified to undergo asymmetric cell
which lies underneath the division, particular proteins localize to distinct regions in a
endodermis. polar manner. Detailed studies of PIN-FORMED (PIN)
Procambium
auxin efflux carriers (which localize in the cell in a polar
A strand of meristematic manner) provide valuable insights into the mechanisms
stem cells that give rise to behind polar localization of proteins in plants 45. However,
the vasculature. what determines these distinct regions and how uniformly
distributed proteins rapidly become polarized are partic-
Periclinal division
ularly difficult problems to address in plants, especially
A type of cell division that
occurs parallel to an adjacent because orthologues of known animal polarity regu-lators,
layer of cells and/or to the such as the partitioning defective–atypical protein kinase
surface of a plant part.
C complex (PAR–aPKC complex), are absent46.
180 | MARCH 2011 | VOLUME 12
© 2011 Macmillan Publishers Limited. All rights reserved
Cell polarity can be instigated by intrinsic factors, such
as the ADP-ribosylation factor–guanine nucleo-tide
exchange factor (ARF–GEF) GNOM (also known as
EMB30). For example, the A. thaliana gnom mutant
shows impaired endosomal recycling and, consequently,
impaired asymmetric division of the zygote and lateral
root founder cells16,47. However, external cues can also
have a role. Indeed, polarity signals might come from
nearby cells, as occurs during maize stomata develop-
ment48, or from the environment, as with light driving the
polarity of fucoid zygotes49. At the level of cell bio-logy,
these fucoid zygotes provide excellent models for
addressing fundamental questions about symmetry
breaking15,50 (BOX 2; FIG. 3c). Localized increases in Ca2+
have been shown to be essential for the polarization
process in Fucus serratus49,51,52, indicating an integral role
for Ca2+ gradients. In plants, however, the lack of good
sensors has hampered the unequivocal demon-stration of
intracellular gradients during asymmetric cell division,
and future studies of phytohormone and ion gradients on a
cellular level will need to use new and more-sensitive
reporters.
From a mechanistic point of view, the plant cyto-
skeleton represents a crucial element in guiding intra-
cellular traffic and facilitating a polar distribution of
proteins before cells divide. Actin probably plays a key
part, and actin patches have been found in young
Fucus distichus zygotes shortly after fertilization53 and
subsidiary mother cells during maize stomata develop-
ment48. These actin patches are likely to serve as a
guide for exocytosis and for the localization of ion
channels in F. distichus, which could be involved in
generating gra-dients54, and also as a site for migration
and anchoring of the nucleus in maize55.
In higher plants, such as maize, the Leu-rich repeat
(LRR) receptor-like kinase PANGLOSS 1 (PAN1) seems
to be involved in nuclear polarization and actin-patch
formation48. PAN1 is a co-receptor for directional guard
mother cell-derived signals that promote the polarization
of subsidiary mother cells, and is also involved in pre-
mitotic polarization of cells48 (FIG. 2f). It localizes in a
polar manner to establish the division axis before
asymmetric cell division during stomata development48.
Also during stomata development, but in A.thalian
a, BREAKING OF ASYMMETRY IN THE
STOMATAL LINEAGE (BASL) marks an intrinsic
polarity during meristemoid mother cell division and
seems to not respond to a stomata-derived signal7 (FIG.
3d). Although it localizes at the periphery in the large
daughter cell, BASL displays nuclear localization in
the small daughter cell after asymmetric cell division.
The precise function and the functional significance of
BASL’s dual localiza-tion are unknown; however, it
seems that BASL is func-tional on the plasma
membrane but is sequestered in the nucleus7.
Positioning of the nucleus. Polar positioning of the vacu-
ole and nucleus, and of a large portion of the cytoplasm,
often precedes morphologically visible asymmetric cell
division and becomes clearly visible in elongating
zygotes12, lateral root founder cells11,37 (FIG. 3e) and
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 REVIEWS

C 8GIGVCVKXGEGNN G

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/KETQURQTG 2QNCTK\GFOKETQURQTG )GPGTCVKXGEGNN H )/% 5/% 5WDUKFKCT[EGNN
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2GTKE[ENG
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'RKFGTOKUNCVGTCNTQQV
ECRKPKVKCN
'RKFGTOKU
.CVGTCN
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Figure 2 | Typical asymmetric cell divisions in plants. a | During pollen development in Arabidopsis thaliana, the
microspore divides asymmetrically to give rise to a large vegetative cell and a small generative cell that then divides
symmetrically, producing two sperm cells. b | Asymmetrically divided Fucus distichus zygote. The arrow indicates the
division plane. c | Asymmetric divisions during A. thaliana embryogenesis. From left to right: zygote, octant cell stage and
hypophysis division. d | Lateral root founder cell division in A. thaliana. The central core contains pericycle cells that divide
asymmetrically into equally sized daughter cells with different identities (brown and blue, right panel). e,f | Schematics of
stomata development. A. thaliana stomatal lineage is initiated in the meristemoid mother cell (MMC), which divides
asymmetrically to form the meristemoid (e). Maize cells that are organized in a file divide asymmetrically upon polarization,
and one daughter cell differentiates into a guard mother cell (GMC). Subsidiary mother cells (SMCs) divide asymmetrically
towards the guard mother cell to produce subsidiary cells. g | Schematics of A. thaliana main root apical meristem, with
asymmetric divisions for cortex/endodermis, columella and epidermis/lateral root cap stem cells.
The cortex/endodermis stem cell divides anticlinally to generate a cell that will divide periclinally to give rise to an
endodermal and cortical daughter cell. Asymmetric cell division of columella stem cells gives rise to a daughter
cell that will differentiate and will be marked by starch (blue dots). Epidermis/lateral root cap stem cells generate
root cap cells and epidermal cells by alternating periclinal and anticlinal divisions, respectively. F‑actin, filamentous
actin; PAN1, PANGLOSS 1. Image in part a is modified, with permission, from REF. 14. © (2009) Oxford University
Press. Image in part b is reproduced, with permission, from REF. 148 © (1996) The Company of Biologists. Images
in part c are reproduced, with permission, from REF. 149 © (2007) Global Science Books.

Symplastic movement
Movement through the
continuous connection
of cytoplasm through
plasmodesmata.
Auxin response factor
A transcription factor that
regulates auxin-responsive
gene expression, the activity
of which is repressed upon
heterodimerization with
AUXIN/INDOLE-3-ACETIC
ACID repressor proteins.
microspores56 (FIG. 2a) in A. thaliana and in germinating
single- celled fern spores57,58 (BOX 2). This raises the
question of whether coordinated nuclear migration is a
prerequisite to obtain distinct cell identities after asym-
metric cell division. The requirement for correct posi-
tioning of nuclei is clear in female gametophytes, in which
aberrant positioning compromises correct cell specifi-
cation, resulting in non-viable female gametophytes59.
However, cell specification in female gametophytes
develops in the absence of asymmetric divisions, so it
is unclear whether nuclear migration is also required
during asymmetric cell division.
Nevertheless, correct positioning of nuclei does seem
to be necessary for cell fate specification during lateral
root initiation. In this case, owing to the specific divi-sion
pattern that is required to generate a central core of small
cells during lateral root initiation19, nuclei of neigh-
bouring lateral root founder cells migrate towards each
other before division, and lateral root initiation takes place
only when both founder cell nuclei are positioned at the
common cell boundary of those two founder cells 11,37
(FIGS 2d,3e). Very little is known about specific molecular
regulators of nuclear positioning, but micro-tubules, and
not actin filaments, seem to be involved.

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© 2011 Macmillan Publishers Limited. All rights reserved
C GURQPUG D 2GTKE[ENG G 2GTKE[ENG molecular players involved in preprophase band forma-
#WZKPPPGKIJDQWTKPITEGNNU tion and positioning of the mitotic spindle65. Because
REVIEWS phragmoplasts are not guided to the asymmetric cell divi-
sion site, the shapes of subsidiary, silica and cork cells are
abnormal and often distort the regular shape of the
6/1 surrounding cell files65. DISCORDIA 1 (DCD1) encodes a
/QDKNG
#WZKPT VTC KQP putative B” family regulatory subunit of the PROTEIN
GURQPUGEGNN FCWIJVGT
PPGKIJDQWTKPI PUETKRVQT! 5OCNN
*[RQRJ[UKU HQWPFGTEGNNU EGNN PHOSPHATASE 2A (PP2A) complex, and its homologue
.CVGTCNTQQV in A. thaliana is FASS (also known as TON2), which is
required for preprophase band formation66,67. Although the
5OCNN function of DCD1 in preprophase band formation is
FCWIJVGT
crucial during asymmetric cell divisions, it is most likely
EGNN
that DCD1 does not act as a specific regulator for asym-
. IG
metric cell division. This is because it acts redundantly
EGNN with ALTERNATIVE DISCORDIA 1 (ADD1) to regu-
late preprophase band formation during symmetric cell
divisions in the maize leaf epidermis66.
In animals, positioning of the mitotic spindle is
E0GYN[HGTVKNK\GF JCȎGTHGTVKNK\CVKQP F involved in determining the fate of the daughter cells,
as misoriented spindles lead to disturbed segregation of
plasma membrane-associated cell fate determinants3. In
the moss Physcomitrella patens, the plane of the first
cell division of stem cells (perpendicular or oblique to
the plane of growth) is required to discriminate
between sec-ondary filaments (which give rise to a
filamentous, planar body plan) and bushy shoots
(.&*2 (.&*2 R$#5.s)(2s$#5.
0CVWTG4GXKGYU^/QNGEWNCT%GNN$KQNQI[ (which generate a body plan in three dimensions)68.
Figure 3 | Key events before asymmetric cell divisions. a | Cell specification requires the
mobile transcription factor TARGET OF MONOPTEROS 7 (TMO7) in the hypophysis, and an Cell fate specification
auxin response (light pink) in the upper neighbouring cells. Following asymmetric cell division of
Segregation of cell fate determinants to generate two cells
the hypophysis, a small upper and a large lower cell can be observed. b | Auxin response in the
neighbouring protoxylem cells is required to specify lateral root founder cells in the pericycle; with different identities can occur through several mecha-
however, it is currently unclear whether a mobile transcription factor is also involved in this nisms, some of which are well studied in animal model
process. c | Polarity establishment upon fertilization in the Fucus distichus zygote, as revealed systems69: asymmetric mRNA localization, transcriptional
through labelling with fluorescent‑dihydropyridine (FL‑DHP), which binds to calcium channels. d repression, differential protein stability and localization,
| Localization of BREAKING OF ASYMMETRY IN THE STOMATAL LINEAGE (BASL) tagged
with green fluorescent protein (GFP), which is strong at the periphery (yellow) of the large
and even differential DNA-strand inheritance. In addi-
daughter cell and nuclear (green) in the small daughter cell. e | Asymmetrically divided lateral tion, an interesting observation comes from studies on the
root founder cells, with the large daughter cells just before a second asymmetric division, multicellular green alga Volvox carteri, in which it is not
displaying polar nucleus and cytoplasm, and a large vacuole. Small daughter cells and large only the segregation of cell fate determinants but also the
daughter cells are indicated. Images in part c are modified, with permission, from REF. 50 ©
(1996) The Company of Biologists. Image in part d is reproduced, with permission, from REF. 7 ©
actual cell size after asymmetric division that determines
(2009) Elsevier. cell identity70.

Asymmetrically distributed and expressed fate deter-

Auxin
A plant hormone that regulates
various aspects of plant growth
and development.
Lateral root founder cell
A pericycle cell that initiates
lateral root primordia.
Protoxylem
The first-formed xylem that
develops from the procambium.
PAR–aPKC complex
(Partitioning defective–atypical
protein kinase C complex). Part
of an evolutionarily conserved
molecular cassette, which has
fundamental roles in cell polarity
and many other biological
contexts in animals.
For example, during pollen development, the A. thal-iana
MICROTUBULE ORGANIZATION 1 (MOR1; also
known as GEM1) and its tobacco orthologue TOBACCO
MICROTUBULE BUNDLING POLYPEPTIDE OF 200
kDa (TMBP200) are required for nuclear positioning
before asymmetric cell division, and mutation of these
proteins leads to defects in the male germline60,61.
Positioning of the preprophase band and spindle. Early
in the cell cycle and before division of the nucleus, plants
select a division plane, which is marked by the pre-
prophase band (FIG. 1a). Although candidate molecular
players were recently identified in A. thaliana, little is
known about the polarizing mechanism determining the
site of preprophase band formation62–64.
Maize discordia mutants, which have abnormal
stomata, cork and silica cells in their leaves owing to defects
in asymmetric cell division, could shed some light on the
minants. In plants, only a few genes that are differen-
tially expressed after asymmetric cell division have
been described1. The importance of differential
expression is illustrated by the fact that asymmetric
expression of germ- specific and sperm-cell-specific
genes during pollen development in A. thaliana and
Lilium longiflorum (trumpet lily) is required for the
formation of viable and functional pollen71–75.
Following the initial asymmetric zygote division in A.
thaliana, the identities and cell division patterns in the
basal and apical cell lineages are determined by differ-
entially expressed transcription factors and other proteins.
Specifically, WUSCHEL -RELATED HOMEOBOX 2
(WOX2)76,77, MP and the gene encoding its inhibiting
protein BODENLOS (BDL; also known as IAA12)78–80, and
PIN1 (REF. 81) (apical in the two-cell-stage embryo) are
expressed in the apical cell. By contrast, WOX8 (REFS 76,77)
and PIN7 (REF. 81) are expressed in the basal cell. The
MAPK kinase kinase YODA (YDA) is also involved in

182 | MARCH 2011 | VOLUME 12 www.nature.com/reviews/molcellbio

© 2011 Macmillan Publishers Limited. All rights reserved
 REVIEWS

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Figure 4 | Asymmetrically expressed determinants after asymmetric cell division, and the role of cell cycle activity.
a | Distinct pathways specify the fate of the apical (yellow) and basal (green) cell following zygote division in Arabidopsis
thaliana. The identities and cell division patterns in these cell lineages are determined by: the differentially expressed
transcription factors WUSCHEL-RELATED HOMEOBOX 2 (WOX2), WOX8, WOX9 and MONOPTEROS (MP; also known
as ARF5); the MP-interacting protein BODENLOS (BDL; also known as IAA12); the PIN-FORMED 7 (PIN7) auxin efflux
carrier; and the mitogen‑activated protein kinase (MAPK) kinase kinase YODA (YDA), along with its downstream signalling
components MAPK3 and MAPK6. b | Well‑timed cell cycle progression and asymmetrically expressed regulators are
crucial during pollen development in A. thaliana and the lily. GERMLINE SILENCING FACTOR (GRSF) in the lily is present
in the vegetative nucleus, in which it represses male germline‑specific transcription (blocked arrow), whereas it is absent
from the generative nucleus. The SKP1–cullin 1–FBL17 (SCFFBL17)‑dependent degradation of the cell cycle inhibitors
KIP‑RELATED PROTEIN 6 (KRP6) and KRP7 releases CYCLIN-DEPENDENT KINASE A;1 (CDKA;1) in the generative
cell of A. thaliana. The germline‑specific protein DUO1 activates (among other proteins) CYCLIN B1;1 (CYCB1;1), a
CDKA;1 regulatory subunit that is involved in cell cycle progression.

Female gametophyte
A multicellular haploid
structure that develops into
an embryo and endosperm
after fertilization.
Silica cell
A short cell that posseses a
silica body (phytolith) in the
epidermis of grasses.
Phragmoplast
A plant-specific cytoskeletal
structure that consists of two
sets of parallel microtubules
and actin filaments, between
which the cell plate forms by
transport of cell-plate forming
vesicles to the centre.
promoting both zygote elongation and suspensor fate82
(FIG. 4a). Despite similarities between the phenotypes of
wox mutants and yda mutants, namely a reduced zygote
elongation and a more symmetric zygote division, WOX
and YDA signalling do not seem to act in a linear path-
way76. YDA acts by activating its downstream signalling
components MAPK3 and MAPK6 (REF. 83), and WOX sig-
nalling is thought to be connected to the auxin response,
which is often associated with the small cell during asym-
metric cell division45,81,84, by regulating PIN-dependent
auxin accumulation in the small apical cell76.
In addition, numerous genes are unequally expressed
in, and/or segregated to, the outer cells during A. thal-iana
embryogenesis, at the moment of protoderm forma-tion.
These include the genes encoding the transcription factors
PROTODERMAL FACTOR 2 (PDF2)18,85 and
ARABIDOPSIS THALIANA MERISTEM LAYER 1
(ATML1)18,86 and the kinase ARABIDOPSIS CRINKLY 4
(ACR4)87,88. Other genes have been shown to be une-qually
expressed in the inner cells, for example ZWILLE (ZLL;
also known as PNH)17,89 , which is a member of the
ARGONAUTE family, MP and BDL18,78. How these
components are interconnected to give rise to the outer
and inner tissues is still unknown. Later in embryo devel-
opment, WOX5 (REF. 77) and SCARECROW (SCR)90 are
expressed by the specified hypophysis and after asymmet-
ric cell division by the lens-shaped cell. Although WOX5
is required only to a limited extent for quiescent centre-
specific gene expression, it plays a major part in stem cell
maintenance after embryogenesis91.
Aside from transcription factors, differential expres-
sion of peptide hormones and/or receptor-like kinases
in one daughter cell after asymmetric division provides
positional information. This mechanism is clearly
important for positioning of stomata40,92 and lateral
roots19, and orienting cell division planes during
vascular development93–95.
Control of differential distribution and expression of
determinants. The asymmetry in expression patterns
can be due to specific gene expression and/or repres-
sion. Indeed, transcriptional regulation is known to be
essential to guide asymmetric cell division in ani-mals.
In Caenorhabditis elegans, the mediator complex,
which is essential for the transcription of RNA poly-
merase II-dependent genes, represses the transcription
of WNT target genes to install asymmetry during the
development of T blast cells96. Interestingly, this might
be conserved in plants, as MED12 and MED13, which
are components of the mediator complex, affect A.
thal-iana embryo patterning, possibly through
transiently repressing a transcriptional programme that
interferes with this process97.
Transcriptional repression is also observed during
pollen development. In this case, the gene expression
mode of vegetative cells is the default developmental
pathway98 , but a transcriptional repressive mechanism is
crucial for correct germ cell differentiation. The
GERMLINE SILENCING FACTOR (GRSF) of lily is
present in the vegetative nucleus and can therefore repress
male germline-specific transcription, whereas it is absent
from the generative nucleus, allowing the expres-sion of
male germline factors99 (FIG. 4b). Furthermore, cell-specific
gene expression can be determined or maintained through
transcription factor activity. In root stem cell niches,
SOMBRERO (SMB) negatively regu-lates FEZ and
restricts its expression to root cap stem cells, where it
promotes root cap-forming cell divisions22.

NATURE REVIEWS | MOLECULAR CELL BIOLOGY VOLUME 12 | MARCH 2011 | 183

© 2011 Macmillan Publishers Limited. All rights reserved
REVIEWS
In addition, a positive feedback loop between the mobile
transcription factor SHR and SCR, which requires
SHR for its expression in the endodermis, induces
endodermal cell fate35.
Furthermore, sequential transient induction of tran-
scription factors can be involved during asymmetric cell
division, as occurs in Drosophila melanogaster dividing
neuroblasts100,101. Although at present largely specula-
tive, a similar sequence of events could be imagined
during A. thaliana lateral root initiation, during which
consecutive expression of ARFs and/or their targets, and
the overlay of the transcription factor profiles in differ-
ent daughter cells, gives rise to a specific cell type11,102.
Sequential transient induction of transcription factors
may also occur in stomata development, during which
three bHLH transcription factors have distinct and
sequential roles103,104, and the requirement for sequential
steps in cell fate determination is apparent.
The aforementioned examples suggest direct trans-
criptional control may regulate asymmetric gene expres-
sion. This implies that there are specific promoter
elements in downstream target genes that could be tar-
geted; indeed, a promoter element that drives the expres-
sion in the basal lineage of the embryo was identified
in several species105–107. However, further investigation
is required to identify whether it is targeted by WOX
transcription factors, YDA signalling and/or currently
unknown players.
Another mechanism for asymmetric distribution of
determinants is mRNA partitioning before cell division.
This is well investigated in animals108–110 but has not yet
been described in plants. However, mRNA partitioning
has been shown in single-celled F. distichus zygotes, in
which filamentous actin (F-actin) mRNA localizes at the
thallus pole9.
In addition to intrinsic factors determining differen-
tial expression of determinants, extrinsic factors have a
crucial role. In this respect, the paternal interleukin-1
receptor-associated kinase protein SHORT SUSPENSOR
(SSP) triggers zygotic YDA activity upon fertilization,
providing a temporal cue for the regulation of asymmetric
cell division111. In addition, auxin and peptide hormones,
such as CLAVATA3/ESR-RELATED 40 (CLE40), affect
gene expression profiles in adjacent cells112,113, and mobile
transcription factors target specific genes in the cells that
they move into114.
Finally, it is possible that additional levels of control to
the above mechanisms of asymmetric cell division exist.
First, SCHIZORIZA (SCZ), a member of the heat-shock
transcription factor family, is cell-autonomously and
non-cell-autonomously required for cell fate specifica-
tion in several tissues in A. thaliana115–117. Second, the
zinc-finger proteins JACKDAW (JKD) and MAGPIE
(MGP) regulate the range of action of SHR and SCR, as
well as the tissue boundaries and asymmetric cell division
in A. thaliana118.
SCF
Cell cycle progression and termination
(SKP1–cullin–F-box).
A ubiquitin protein ligase
In animals, the cell cycle has been linked to asymmetric tide hormone CLE40 and affects the WOX5 expression
complex that functions in localization of cell fate determinants, but cell division
protein degradation. per se is not essential for a cell to adopt a particular fate 101,119. a number of asymmetric cell divisions and relay this to
184 | MARCH 2011 | VOLUME 12
© 2011 Macmillan Publishers Limited. All rights reserved
Nevertheless, the regulation of asymmetric cell divi-
sion needs to be precisely coordinated with cell cycle
progression120.
Coordinating asymmetric cell division and the cell cycle.
During A. thaliana pollen development, asymmetric
cell division and correct cell identity specification are
crucial to generate functional sperm cells and are tightly
connected to cell cycle progression and activity. The plant
Cdc2 homologue CYCLIN-DEPENDENT KINASE A;1
(CDKA;1), a general cell cycle regulator with a role in
embryo patterning121, is involved in the proliferation
of generative cells in male gametogenesis122 and needs
to be repressed in vegetative cells123. It has also been
shown that the specific SKP1–cullin 1–FBL17 (SCFFBL17)-
dependent degradation of the cell cycle inhibitors KIP-
RELATED PROTEIN 6 (KRP6) and KRP7 plays a part
in cell cycle control by releasing CDKA;1 in the genera-
tive cell, allowing cell cycle progression124. Furthermore,
the germline-specific protein DUO1 activates numerous
genes, including CYCLIN B1;1 (CYCB1;1), which is a
CDKA;1 regulatory subunit that is involved in cell cycle
progression74,123 (FIG. 4b). In addition, sidecar pollen
(scp) mutants display delayed entry into mitosis and
alterations in the orientation of cell division; this sup-
ports a role for SCP, which encodes LATERAL ORGAN
BOUNDARIES DOMAIN (LBD; also known as ASL), in
correct timing and orientation of microspore division 125.
Overall, correct timing and location of expression of
several core cell cycle genes are crucial for proper male
gametophyte development14.
During asymmetric divisions that give rise to
cortex and endodermis, SHR and SCR directly activate
CYCD6;1, and CDKB2;1 and CDKB2;2 act downstream
of the SHR and SCR network126, providing a connection
between master regulators and cell cycle progression
in embryonic and main roots. In addition, studies on
RETINOBLASTOMA-RELATED (RBR) showed its
requirement for stem cell divisions in the root apical
meristem127. Other indications of specific cell cycle regu-
lators involved in asymmetric cell divisions come from
analyses of lateral root initiation19,128,129, during which the
absence of KRP2-mediated prevention of cell cycle G1–S
progression was shown to be regulated by auxin and to
be crucial for lateral root initiation and thus asymmetric
division of the xylem-pole pericycle128.
Termination of the cell division programme. Because
asymmetric cell division is intended to generate organ-
ized cell types, tissues and organs after completion of
the cell division programme, in several cases at least
one of the resulting daughter cells must terminate cell
division to prevent proliferation or irregular clustering
of organs. During lateral root initiation and stem cell
division in the root apical meristem, ACR4 restricts
the number of asymmetric, formative cell divisions19.
Although the underlying mechanism is unknown, ACR4
is, at least in the main root tip, a likely target of the pep-
domain112. As such, ACR4 could perceive a signal after
www.nature.com/reviews/molcellbio

C D E Common mechanisms and regulators
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Figure 5 | Common regulatory mechanisms during asymmetric cell division.
a–c | Schematics for a 90 ° change in division plane following asymmetric cell division in a
single lateral root founder cell following a series of anticlinal asymmetric cell divisions (a), the
apical cell following the asymmetric cell division of the zygote (b), and the daughter cell
following cortex/endodermis stem cell division (c). d | Schematical representation of common
pathways. YODA (YDA) acts on zygote and stomata development. BODENLOS (BDL; also
known as IAA12) and MONOPTEROS (MP; also known as ARF5) act on embryo development
and lateral root initiation; MP also acts on the root apical meristem stem cell niche.
ARABIDOPSIS CRINKLY 4 (ACR4) acts on protoderm development in the embryo, on lateral
root initiation and on columella development in the root apical meristem. Auxin transport
mediated by PIN‑FORMED (PIN) proteins and GNOM (also known as EMB30) affect lateral root
initiation and (early) embryo development.
the adjacent cells, resulting in termination of asymmetric
cell division. A similar role was proposed for SMB, which
represses FEZ expression in columella daughter cells to
prevent further stem cell divisions22. If and how the FEZ
and SMB cross-regulatory feedback loop is connected to
ACR4-dependent signalling is currently unclear.
Similarly to lateral root founder cells, which divide a
limited number of times asymmetrically, meristemoids
display stem-cell-like properties. During the asym-metric
division of meristemoids, the transcription factor MUTE,
which is expressed only by meristemoids that have
undergone a few rounds of asymmetric cell divi-sion, acts
intrinsically to trigger differentiation104. RBR also seems
to have a role in terminal differentiation by promoting exit
from the cell division programme of meristemoids and
entry into cell differentiation130.
NATURE REVIEWS | MOLECULAR CELL BIOLOGY
© 2011 Macmillan Publishers Limited. All rights reserved
REVIEWS
Various developmental processes require asymmetric cell
division; but are similar, or even the same, mechanisms
and/or conserved molecular players involved? Below, we
compare asymmetric cell division across different pro-
cesses and specifically between the embryo and root and
the embryo and stomata.
Similarities across different processes. On the mecha-
nistic level, one recurring phenomenon in A. thaliana
asymmetric cell division is a 90 ° change in orientation
of the division plane following the first asymmetric
division. During lateral root initiation, the division
plane shifts from anticlinal in the lateral root founder
cells to periclinal in the small central cells19 (FIG. 5a).
Furthermore, following the first transverse division of
the A. thaliana zygote17, the small apical cell divides
longitudinally (FIG. 5b), and, at a later stage of embryo
development, protoderm formation and establishment
of a functional root meristem follows a similar change
of division plane16,17. The asymmetric cell divisions
required to generate the cortex and endodermis also
undergo a change in cell division plane1,34 (FIG. 5c) . An
additional example of a mechanistic similarity is that
both ACR4-dependent signalling during lateral root ini-
tiation19 and the MAPK signalling system controlled by
YDA during stomata development42 seem to have dual
functions, both promoting and restricting asymmetric cell
division or differentiation (see below).
At the molecular level, numerous regulatory proteins
are used to control similar mechanisms but give rise to a
different cell type or organ (FIG. 5d). However, the involve-
ment of the same key regulators in different processes
might be restricted to one level of control, and subsequent
downstream cascades might be totally different.
Embryo versus root. During early embryo
development, asymmetric cell divisions in the zygote
and hypophysis are controlled by MP and its inhibitor
BDL6,79,80. As a consequence, loss-of-function mp or
gain-of-function bdl mutants display aberrant, ectopic
divisions in the early embryo and fail to establish a
root meristem6,79,80. During lateral root initiation, both
mp and bdl mutants display similar features, namely
ectopic cell divisions in the pericycle, which is —
based on analogy — likely to be the result of incorrect
cell identity prior to or after asymmetric division of
lateral root founder cells102 (FIG. 5d). In addition, GNOM-
and PIN-dependent auxin transport are similarly involved
in early embryo development and lateral root initiation,
regulating cell identity and subsequently preventing
excessive cell divisions19,47,81,84 (FIG. 5d).
Interestingly, MP is also involved in abscisic acid
(ABA)-dependent regulation of stem cell maintenance
in the root apical meristem in A. thaliana131. This
suggests that the same AUXIN/INDOLE-3-ACETIC
ACID–ARF module controls a similar process (that is,
preventing wrongly positioned and/or ectopic cell
divisions after the initial asymmetric cell divisions)
during zygote division, lateral root initiation and root
apical meristem stem cell maintenance (FIG. 5d).
VOLUME 12 | MARCH 2011 | 185
REVIEWS

ACR4 also has a similar role in the control of formative
cell divisions both during lateral root initiation and in the root
apical meristem19 (FIG. 5d). In addition, at the derma-togen
stage, ACR4, which is expressed from the eight-cell stage
onwards in the apical lineage, becomes restricted to the
daughter cell that gives rise to the protoderm87,88. In the same
way, during lateral root initiation, ACR4 expression is limited
to the small, central core of daughter cells that will contribute
to the new primordium19.
Embryo versus stomata. YDA acts as part of a molecu-lar
switch controlling cell identities in the epidermis (to
regulate stomata formation) and promoting extra-
embryonic fate82,132 (FIG. 5d). YDA activity, however, must
be downregulated to allow cells to enter the stomatal
lineage, and its normal activity is required to maintain the
balance of proliferation versus differentiation (into guard
mother cells) in the meristemoids132. In addition, YDA is
active in the zygote and remains active in the basal
lineage, where it promotes extra-embryonic cell fates, but
is inactivated in the apical lineage to allow the
establishment of embryonic cell fates82.
Furthermore, it seems that some of the downstream
signalling components of YDA signalling are also con-
served in embryos and cells committed to the stomatal
lineage. Indeed, MAPK3 and MAPK6 are involved in sto-
mata development and also have roles in the division of
the zygote (FIG. 4a), giving rise when mutated to a yda-like
phenotype with an equal apical and basal cell83.
Concluding remarks and perspectives
Over the past few years, several new players in plant asym-
metric cell division have been identified. Although plants
seem to lack some signalling components that have been
identified in animals46, they still possess a broad range of
components that could carry out these functions, such as
mobile transcription factors5,34, proteins that localize in a polar
manner7, plant hormone maxima45,133 and a wide range of
ligand–receptor-like kinases29. In addition, local changes in
cell growth and in control of cell wall elasticity can result in a
feedback mechanism affecting cell identity, which might
occur, for example, during lateral root ini-tiation and stomata
development7,134, a speculation that should be explored
further. As plant cells do not migrate
and are fixed within a cell wall, a prominent cell-to-
cell communication system is required, which might
explain the diversity of non-cell- autonomous control
mecha-nisms. The identification of new components
could be tackled through targeted reverse genetics
studies, as was done when the function of ACR4 in the
root was identi-fied19, or through sensitized mutant
screens, as has been done for stomata development135.
Some mechanisms that drive asymmetric cell
division in animals might also work in plants, but these
still need to be investigated. The possible mechanisms
include: asymmetric localization of cell fate
determinants by differential regulation of mobility and
protein stability in different parts of the cell;
phosphorylation-dependent asymmetric localization of
cell fate determinants; and endosome-dependent
unequal segregation of activated ligand–receptor
complexes to ensure that signalling starts immediately
after asymmetric division in one of the daughter cells46.
Because the outcome of asymmetric cell division
differs for each process (BOX 1), another important aspect
that needs to be addressed is whether specific processes
also have unique ways to obtain two distinct cells. It is not
clear whether the fact that the same proteins are involved
in different processes reflects that they have a general role
in asymmetric cell division or, instead, that they control
unique downstream signalling cascades.
In higher plants, asymmetric stem cell divisions have
been well investigated in the root136 but not in shoot apical
meristems137,138, despite a known role for asym-metric cell
division in P. patens shoot morphogenesis68 (BOX 2). In
addition, A. thaliana TONSOKU (TSK), a protein that
shows some similarity to animal proteins involved in
asymmetric cell division, such as Partner of Inscuteable,
hints towards a role of asymmetric cell divi-sion in the
shoot meristem139. Based on these examples, it is clear that
the importance of asymmetric cell division for the
functioning of the shoot apical meristem needs to be
analysed further.
Finally, because the loss of control of asymmetric cell
divisions in animals140 and plants19,79,102,141 can give rise to
cancer and aberrant divisions, respectively, it will be
crucial to study the connection between terminal
differentiation and cell cycle activity in more detail.

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Acknowledgements
We thank G. Den Herder, D. Van Damme and two anonymous
referees for critical reading of the manuscript and useful
suggestions, W. Grunewald, L. Smith, R. Quatrano, D. Twell, M.
F. Njo, R. De Rycke and J. Dong for providing pictures and G. Van
Isterdael for preparing the figures. We apologize to those
colleagues whose work could not be included because of space
restrictions. This work was supported by the Biotechnology and
Biological Sciences Research Council, UK (BBSRC David Phillips
Fellowship to I.D.S.); the Research Foundation — Flanders,
Belgium (postdoctoral fellowship to I.D.S.); and grants from the
Interuniversity Attraction Poles Programme (P6/33 and P5/13),
initiated by the Belgian State Science Policy Office (BELSPO).
Competing interests statement
The authors declare no competing financial interests.
FURTHER INFORMATION
Ive De Smet’s homepage: http://www.nottingham.ac.uk/
biosciences/divisions/plantcrop/people/Ive.De_Smet Tom
Beeckman’s homepage:
http://www.psb.ugent.be/roots‑projects
ALL LINKS ARE ACTIVE IN THE ONLINE PDF
www.nature.com/reviews/molcellbio
 ONLINE ONLY

Author biographies TOC

Ive De Smet carried out his doctoral work with Tom Beeckman at
the VIB Department of Plant Systems Biology, Ghent University, 000 Asymmetric cell division in land plants and
algae: the driving force for differentiation
Belgium, and then did his postdoctoral studies with Gerd Jürgens at
the Centre for Plant Molecular Biology, University of Tübingen, Ive De Smet and Tom Beeckman
Germany, and the Max Planck Institute for Developmental Biology, Asymmetric cell division is essential in many
Tübingen. Currently, his newly established research group at the organisms, as it generates different cell types
University of Nottingham, UK, focuses on ligand–receptor-like and maintains stem cell pools. The
kinase interactions in root development. identification of key molecular players, and a
comparison with the pathways in animals,
After completing degrees in botany in the Biology Department of allows a better mechanistic understanding of
Ghent University, Tom Beeckman joined the cell cycle group of asymmetric cell division in plants and algae.
Dirk Inzé as a postdoctoral researcher in the Plant Genetics
Department at the same university. Currently, he is leading his own
group on root development as principal investigator of the VIB Subject categories
Department of Plant Systems Biology. His team focuses on the Cell Signalling
initiation of new organs in plant roots with the central question of Development
how the cell cycle and cell dif-ferentiation are integrated. Plant Cell Biology
Cell Polarity
Online Summary
• Asymmetric cell division is essential in many organisms to
gener-ate cell diversity and tissue patterns and to maintain pools
of stem cells. In plants and multicellular algae, asymmetric cell
division is of particular importance, as their post-embryonic
growth is based on de novo formation of cell types, tissues and
even entirely new organs.
• Daughter cells, which can be initially equivalent or different in size
and/or molecular composition, can achieve different cell fates
through intrinsic or extrinsic factors that convey positional infor-
mation. These seemingly distinct mechanisms can rarely be sepa-
rated, and it is becoming clear that every asymmetric cell division
depends on both extrinsic and intrinsic factors simultaneously.
• Asymmetric cell division in plants involves numerous steps:
specification of a subset of cells that will undergo asymmetric
cell division; cellular events (such as establishment of polarity,
polar localization of proteins, establishment of gradients, correct
posi-tioning of the nucleus, polar accumulation of the cytoplasm
and formation of the preprophase band, spindle and cell plate);
and the asymmetrical distribution and expression of cell fate
determi-nants. Together, these control the identity and future
development of both daughter cells into a differentiated tissue or
new organ. However, not all steps are necessarily present in
every asymmetric cell division process.
• In animals, the cell cycle has been linked to asymmetric localiza-
tion of cell fate determinants and, consistently, the regulation of
asymmetric cell division needs to be precisely coordinated with
cell cycle progression in plants as well.
• Various developmental processes require asymmetric cell
division and use similar, or even the same, mechanisms and/or
conserved molecular players.

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