I.

INTRODUCTION • Adult shows no further cell division of somatic tissues

• Small, free-living, soil nematode • Can only grow by cell enlargement
• Location and lineage in every cell in embryo, larva, and
adult is known III. ANALYSIS OF POSTEMBRYONIC
• First animal to have its genome completely sequence DEVELOPMENT
• 19,099 genes
• Generation time: 3 days
• Self-fertilized hermaphrodites IV. EMBRYONIC DEVELOPMENT
• SPERM
• RNA interference: dsRNA complementary to an
- Amoeboid in nature: no flagellum or acrosome
endogenous message can be administered by feeding
• OOCYTES
• Transgenics by injection: required DNA into gonad
- Fertilized BEFORE the first meiotic division
(incorporated as an extrachromosomal element into the
germ cells)
Major Sperm Protein
*not stable because element can be lost at meiosis or mitosis
- Released from a nearby sperm
• Incorporation of transgenes into the genome by
- Will initiate the maturation and germinal vesicle
excision of transposons followed by repair of resulting
breakdown
ds break by DNA synthesis
• Genetic mosaics – made by the spontaneous loss of
• Sperm can enter the oocyte at any position
small, free chromosome fragments
- Entry point of the sperm will determine the posterior
• Possesses 6 Hox genes (do not form true cluster as
region of the zygote
there are some intervening genes)
- SMOOTH POSTERIOR CORTICAL REGION:
• Genes obey rule of colinearity of chromosomal position
point of the sperm entry
and anterior expression limit
- RUFFLED REGION: remaining part
• 2nd gene: ceh-13 (most anterior expression limit)
• Cytoplasmic rearrangement can be observed once both
meiotic division are through
Homologous to anterior Hox genes in other animals
- INTERNAL CYTOPLASM: posterior
• 6 Hox genes:
- CORTICAL CYTOPLASM: anterior
• lin-39
- Both are associated with PSEUDOCLEAVAGE
• ceh-13
formation: does not progress into a complete full
• mab-5
cleavage.
• egl-5
- Result: ASSYMETRICAL EARLY CLEAVAGE
• php-3
• nob-1 Abdominal B
*ceh-13, php-3, nob-1 have
embryonic phenotypes in loss-of-
(posterior class)
function mutants
• Disadvantage: small size of
eggs and tough egg case
Many mutations: maternal effect

II. ADULT ANATOMY

• Highly elongated
• Outer layer: hypodermis
- One cell thick
- Largely syncytial
- Secretes thick cuticle
• Beneath hypodermis: 4 longitudinal bands
(mononucleate muscle cells)
• Tough gut with muscular pharynx and intestine
• Nerve ring surrounds the pharynx, ventral nerve cord,
and tail ganglia
• Main body cavity: pseudocoelom (not lined all around
with mesoderm)
• Gonad opens into mid-ventral vulva
- Cells nearest the vulva mature as sperm
- More distant cells divide, become oocytes
which mature into eggs
• Hermaphrodites: XX
• Males: XO (other X chromosome lost by disjunction
during meiosis)
Male x Hermaphrodite = Outcross
• Shows almost complete invariance of cell lineage (every
individual embryo shows exactly the same sequence and
orientation for every cell division)
• Embryos laid at about 30 cells, hatch at about 14 hours
with 558 cells
• Larva feeds and grows, undergoes 4 molts with 959
somatic cells and about 2000 germ cells
• 2nd stage larva may enter a dormant phase: dauer larva
(when nutrients are short in supply during first larval
stage)
!
• 26 Cell Stage
- Earliest stage where defects are visible
- Only apparent if embryos are raised in α- amanitin
- α- amanitin : RNA II polymerase inhibitor
Posterior P1
- behaves in a reiterated manner keeping P-like
daughter cells (P1,P2, P3, P4) while cutting EMS, C
and D blastomeres
- P4 (final cell): germ cell precursor
Z3: generates all the germ cells of larva and adult
!
Egg
- RNA rich P-Granules
▪ Initially randomly dispersed but it will be
concentrated at the posterior region during
cytoplasm rearrangement
▪ During succesive division: stays in the region
where future P-cells will arise
▪ Fates:
 - P4- germ line - localization may be studied by immunostaining for the protein or
- E- gut by observing the intracellular position of a transgenic GFP
- D- muscle fusion protein by fluorescence microscopy

Protein Biochemical nature Loss-of-function

GASTRULATION
phenotype
- Atypical and prolonged
- Starts at 26 cell stage SKN-1 bZIP transcription factor Too much hypodermis
▪ 2 E cells move into the interior, autonomous
invagination process PIE-1 Zn finger transcription Excess pharynx and
▪ Derivation of myoblast from C and D factor intestine; no germline
▪ Derivayion of pharyngeal cells from Aba
- 300 cell stage : closure of the ventral cleft occurs MEX-1 Cytoplasmic Zn finger Muscle excess
o Small in terms of cell number and protein
invariance: reason behind why all individuals
undergo the same sequence of the cell dividion MEX-3 RNA/protein-binding Muscle excess
o Precision of the cell lineage makes it less protein
useful to define which parts of the embryo
belong to the following germ layers. MEX-5,6 Cytoplasmic Zn finger Muscle excess
▪ ECTODERM: AB, Caa, Cpa proteins
▪ MESODERM: MS, Cap, Cpp, D
▪ ENDODERM: E PAL-1 Homeodomain Posterior defective
• AB: pharyngeal muscle formation: transcription factor
but is known to be mesodermal
• SKN-1 (“skin-1”)
• MS: pharyngeal neurons: but is know - transcription factor of bZIP type and confers an EMS type of
to be ectodermal development on its nuclei
- Development was thought to be mosaic in nature - mRNA is present maternally and is not localized
- When a cell is removed by laser microbeam - protein accumulates only in P1 nucleus, and later in the
irradiation, all of its descendants are lost and there’s descendant P2 and EMS nuclei
no consequence for the development of neighboring - becomes lost after the 12-cell stage
cells - no SKN-1 ➔ lack pharynx and intestine because the E and MS
- blastomeres develop like the C blastomeres (too much skin)
A. REGIONAL SPECIFICATION IN THE EMBRYO - its transcription factor is repressed in P2 by the PIE-1 protein (=
also responsible for repression of all RNA polymerase II-
A. ASYMMETRICAL CLEAVAGES mediated transcription in early germline)
- Requires two processes
o Establishment of cytoplasmic polarity - embryos lacking PIE-1 still have a normal distribution of SKN-1
o Correct orientation of mitotic apparatus protein, but the P2 cell now develops like EMS, because SKN-1
- PAR Proteins is active in both cells
o Partitioning defective
o Key players - mex-1 mRNA is initially ubiquitous but becomes lost from cells
o Screens for maternal- effect lethal mutation other than the P lineage
deranging early cleavage - the protein concentrates in the posterior of the zygote
o Its mammalian and D. melanogaster himologs - MEX-1 appears to prevent SKN-1 from entering AB
are also involved in the acquisition of cell - embryos lacking MEX-1 have SKN-1 in the nuclei of the two AB
polarity and asymmetrical cell division control. daughter cells as well as in P2 and EMS
➔ they have AB descendants developing like the normal MS
▪ PAR- 1 : SerThr kinase, binds non muscle descendants ➔ too much muscle
myosin and found at the posterior cortex of the - embryos lacking both MEX-1 and SKN-1 have a similar phenotype
zygote to that cause by lack of SKN-1 alone, with AB normal but EMS
▪ PAR- 2: cytoplasmic protein with ATP- binding developing like C
and zinc binding (RING) domains. Found at the = AB behavior depends on the absence of SKN-1
posterior cortex of the embryo
▪ PAR- 3 & -6: cytoplasmic proteins containing - pal-1 is a homolg of the Drosophila caudal gene and the
PD2 Domains (Protein-protein recognition). It vertebrate Cdx gene family
forms a complex with an atypical protein kinase - it is needed for posterior development
C (aPKC3). It is associated with the plasma - mRNA is present all over the embryo, but is normally translated in
membrane in the anterior portion of the EMS and P2
zygote. - translation is repressed during early stages, and in AB cells, by
MEX-3
B. MITOTIC ORIENTATION
- MEX-3 acts on the 3’UTR of the pal-3 mRNA
C. DETERMINANTS - the mex-3 mRNA and MEX-3 protein are initially uniform then
Determinants become more abundant in AB cells and are lost after the four-
- in addition to PAR proteins, several other maternally encoded cell stage
proteins have been identified to be responsible for regional - embryos lacking MEX-3 express PAL-1 protein all over and are
specification posteriorized in morphology, with the AB descendants
- mode of action has been deduced from maternal effect mutant resembling the normal descendants of blastomeres C
phenotype, and from effect on their localization of mutating
other genes, including the par genes
- spatial disposition of the determinants is controlled by the PAR
system and PAR-1 is the main effector, acting on the
cytoplasmic proteins MEX-5 and MEX-6 such that they become
localized to the anterior
- this is achieved by an increase in the intracellular diffusion rates
of the MEX proteins following phosphorylation by PAR-1
- MEX-5 and MEX-6 act on MEX-1 and PIE-1 proteins and the P-
granules, to localize them all to the posterior where they direct
the formation of the P lineage of blastomeres
- evidence: absence of PAR-1 = MEX-1, -5, -6 proteins, the PIE-1
protein, and the P-granules are all uniformly distributed
- absence of MEX-5 and -6 proteins = PAR-1 distribution is normal,
but distribution of MEX-1, PIE-1, and the P-granules are all
uniform, showing that PAR-1 normally regulates the
localization of MEX-5 and -6 and they in turn control the
disposition of other components
- MEX-5 and -6 concentrate MEX-3 in the anterior
- absence of PAR-1 = MEX-3 is present all over the embryo
- MEX-3 in the anterior inhibits the production of PAL-1 by
translational control, confining the activity of PAL-1 to the
posterior
- absence of PAR-1 = uniform MEX-3, there is no expression of
PAL-1 and posterior development is defective
D. INDUCTION OF THE PHARYNX
highly muscular organ; contains glands and neurons
- pharynx of adult worm = tube in three sections
- corpus joins the buccal cavity and serves to pump food further in
- isthmus moves food on by peristalsis
- terminal bulb grinds the food finely to prepare it for the intestine
- pharynx arises from descendants of both ABa and MS blastomeres
- the part requiring from ABa requires two successive inductive
signals in order to form
- 1st = repressive and comes from the P2 cell
- 2nd = positive and comes from the descendants of MS
- both signals operate through the Notch pathway, but utilize
different ligands of Notch
- repressive signal prevents formation of pharynx from sister
blastomeres of ABa, ABp
- if the two are interchanged, then ABp will form the anterior
pharynx instead of ABa, showing that position of cell rather
than its lineage is important
- if P2 is prevented from touching ABp then ABp forms pharynx as
well as ABa, showing that there must be normally be a signal
from P2 to ABp that suppresses pharynx formation
- repressive signal = encoded by maternal-effect apx-1 (anterior
pharynx excess) gene
- embryos lacking APX-1 show formation of anterior pharynx from
both AB blastomeres instead of just ABa
- apx-1 codes for a Delta-like ligand
- receptor is encoded by another maternal-effect gene, glp-1
(germ-line proliferation) whose product is a Notch-type
receptor
- embryos lacking GLP-1 also have ABp developing as ABa in most
respects, but unlike apx-1-, glp-1- mutants do not actually go
on to form pharynx from the two equivalent ABa-like
blastomeres
- formation of pharynx is not a default for ABa, but depends on
subsequent positive inductive interaction
- this is shown by the fact that an isolated AB cell does not produce
any pharynx
- also, laser ablation of MS cell between 8 and 12 cells prevents
ABa forming pharynx (showing that its presence is necessary
during this time interval)
- 12-cell stage = the MS blastomeres touches the two ABa grand-
daughters (ABalp and ABara), and emits the 2nd signal
responsible for inducing the pharynx
- in apx-1- embryos, the descendants of the ABp cell that produce
pharynx are ABpra, ABprp, and ABplp, all of which also contact
MS at the 12-cell stage
- receptor for this 2nd signal is also GLP-1, since the mutant
embryos do not form a pharynx, even though in other regards
the 2 AB lineages behave the same
- the glp-1 mRNA is uniformly distributed in the embryo up to the
8-cell stage but the protein is found only in the AB
descendants
- this is because of differential translation regulated by a sequence
in the 3’-UTR of the message, with translation in the posterior
being repressed by a cascade of factors ultimately controlled
by PAR-1
- GLP-1 protein disappears at the 28-cell stage (when there are 16
AB descendants)
- the ligand for GLP-1 expressed by MS is distinct from APX-1
- hence, there is a double requirement for GLP-1, first as the
receptor mediating repression of pharynx formation by the
action of P2 on ABp, and then as the receptor mediating
nmkpositive induction of pharynx formation by the action of
MS on ABa
- these two separate requirements are clearly shown by the
phenotypes of temperature-sensitive mutants of glp-1, kept
for different time periods at the nonpermissive temperature
- nonpermissive temperature given around the 4-cell stage =
phenotype is just like the maternal effect phenotype of apx-1-,
with ABp as well as ABa forming pharynx
- nonpermissive temperature maintained until 12-cell stage =
phenotype is like maternal effect of glp-1 null mutant, with
equivalent cell divisions of ABp and ABa but no subsequent
pharynx formation
- ultimately, formation of pharynx is dependent on zygotically
expressed gene pha-4, encoding a winged helix transcription
factor homologous to FoxA genes important in vertebrate gut
development
- pha-4 is activated by T-box transcription factors, which become
zygotically upregulated in both the ABa- and the MS-derived
parts of the pharynx
- in the ABa-derived part: they are the genes tbx-37 and -38
- MS: the gene tbx-35 = upregulated by the products of the
zygotic genes med-1 and -2 which encode GATA-type
transcription factors and are themselves activated by SKN-1
- PHA-4 is responsible for controlling expression of pharyngeal
genes in all the component cell types of the organ through a
“pharyngeal enhancer”
- among cell-type-specific genes that are activated are hlh-6
(encoding a bHLH factor controlling gland differentiation) and
tbx-2 (controlling muscle differentiation)
- loss-of-function mutant of pha-4 lacks the entire pharynx, both
the part formed from ABa and the part formed from MS
- use of a temperature-sensitive allele shows that there is a
requirement for pha-4 throughout development for both early
and late differentiation events
- level of expression increases progressively during development =
promoters with a high affinity for PHA-4 are turned on early,
and those with lower affinity are turned on later when the
concentration of PHA-4 protein has built up to a sufficient level
- PHA-4 also has functions in gonadal development and affects the
lifespan of the adult worm
E. INTESTINAL DEVELOPMENT
- intestine = 20 cells derived from the E blastomere
- these cells polarize, intercalate with each other, and become
arranged around a gut lumen and joined with junctional
complexes
- developmental specification of the E blastomere depends on the
induction from the P2 cell
- this emits a Wnt-like signal that causes the nearer, posterior, part
of EMS to become E and the further, anterior, part to follow
the default specification of MS
- this may be shown by removing the P2 cell, which causes both
daughters of EMS to resemble MS
- series of mom (more mesoderm) mutants have a similar effect to
loss of P2
- these encode members of a Wnt-like pathway, and it was shown
by mosaic analysis that the signaling components including the
product of Wnt homolog itself (mom-2) were required in the
P2 cell, while the receptor homolog (mom-5) was required in
EMS
- loss-of-function, maternal-effect mutations of these genes will
convert E into a 2nd MS
- the reverse phenotype results from loss of function of pop-1,
which encodes an HMG domain transcription factor similar to
the Tcf and Lef factors in vertebrates
- this converts MS into a second E, suggesting that formation of E
depends on inhibition of POP-1 activity by the Wnt-like signal
- in vertebrates, the Wnt-beta catenin pathway would normally
activate TCL/LEF
- the C. elegans Wnt-like pathway is somewhat different and is
variously called the “Wnt/MAPK pathway” or
“noncanonical Wnt pathway” but these terms are
misleading in that they imply close similarity to similarly
named vertebrate pathways
- C. elegans Wnt-like pathway operates as follows:
- Wnt-like (MOM-2) signals though MOM-5 to activate both a
homolog of beta-catenin (WRM-1) and a SerThr kinase (LIT-1,
for loss of intestine, a homolog of a Drosophila kinase called
NEMO)
- LIT-1 phosphorylates POP-1, and WRM-1 then facilitates its export
from the nucleus
- another distant homolog of beta-catenin, SYS-1 (symmetrical
sisters), become elevated in the prospective E cell
- POP-1 normally represses expression of end-1 and end-3, which
encode GATA factors needed for intestinal development
- in the MS nucleus where POP-1 remains high, these genes are
repressed
- in the presence of an excess SYS-1, POP-1 becomes an activator
of the same target genes
- in the E lineage end-1 and -3 are activated and they bring about
activation of a battery of further genes controlling intestinal
differentiation
- the same mechanism of Wnt-like signaling affecting the ratio of
POP-1 and SYS-1 in the two daughters, operates many more
times in C. elegans development, including formation of the
distal tip cells that control germ-cell proliferation
V. ANALYSIS OF POSTEMBRYONIC
DEVELOPMENT
A. CONTROL OF DEVELOPMENTAL TIMING
Developmental timing- describes the global orchestration of how
developmental events or stages temporally unfold, specified in strict
sequence by a gene regulatory network.
After hatching.. C. elegans undergoes 4 larval stages:
L1- division of intestinal cells
L2- division of lateral hypodermal seam cells
L3
L4- exit from the cycle, fuse to form cuticulur lateral ridges:
alae
(ea. separated from the next by molting)
Heterochronic mutations- can affect multiple
lineages; mutation that disturbs the relative timing of events during
postembryonic development.
a. Lin-4:
- loss-of-function
- causes the L1 cell div. patterns to be repeated (w/ extra
molts)
b. Lin-14:
- loss-of-function
- causes skipping of L1 divisions and occurrence of L2-type divisions
during L1
* loss of both (Lin-4 and Lin-14) shows a Lin-14 phenotype.
* Lin-14 (gene) has gain-of-function mutations that have Lin-4
like effects.
!
Lin-14: encodes a transcription factor and its translation into a
protein is inhibited by the product of Lin-4; encodes a transcription
factor and its translation to protein is inhibited by the product of
Lin-4 (microRNA)
*Lin-4 is expressed during L1, so by the start of L2, translation of
Lin-14 is suppressed.
The gain-of-function alleles of Lin-14- lost the 3’ untranslated
region from the mRNA and are therefore resistant to the inhibitory
action of Lin-4.
Lin-14 is parallel w/ Lin-28 (cytoplasmic binding protein), the loss of
Lin-28 causes the skipping of L2 cell division.
Lin-14 and Lin-28 stimulates each others translation.
!
A similar switch occurs at the end of L2.
Hbl-1: homolog of Hunchback, controls the division of cells during
L2.
* if all three microRNAs are removed, L2 cell divisions are repeated.
*If one microRNA is overexpressed before L2, L2 is skipped due to
premature removal of Hbl-1.
!
At the end of the larval stages, the loss-of-function of Let-7, causes
repetition of the last larval stage events.
Loss-of-function of Lin-41 causes adult transition at L3 instead of
L4.
Let-7: inhibits Lin-41(cytoplasmic protein)
Lin-41: inhibits Lin-29 (triggers exit from the cell cycle and cell
fusion.
Normally let-7 expression is high during L3 and suppresses Lin-41
at the end of L4.
How does this set of repressive interactions build up into a
developmental timing controller?
No answer yet- clue from the Lin-42.
Lin-42: contains mRNAs and proteins which are expressed in a
periodic manner, high in intermolts, low during molts.
- protein is located at the nuclei, which is homologous to Per
(Drosophila): which have a central role of the circadian rhythm.
- loss-of-function of Lin-42 causes repetition.
- expression of Lin-42, provides a gating mechanism for the larval
stages of C. elegans.
B. THE VULVA
The Vulva
• Epidermal structure in larval life
• Mid-ventral opening of gonad
• For egg laying and mating
• Controlled by an Epidermal Growth Factor (EGF) called
anchor cell
• Arises from 3 ectodermal cells:
o P5p – makes 7 vulval descendants
o P6p - makes 8 vulval descendants
o P7p – makes 7 vulval descendants
4th larval stage:
• 22 cells undergoes movements to make vulva
• P3p, P4p, P8p cells are competent to make vulva, but
normally enter the syncytial hypoderm
Formation of 8 cells - 1° fate ! P6p
Formation of 7 cells - 2° fate !P5p, P7p
Formation of 2 cells - 3° fate !P3p, P4p, P8p
Hermaphrodites:
• Able to reproduce w/o vulva
• Possible to screen for vulval defects w/c prevents egg
laying
• Viable mutations – hypomorphic with the corresponding
null alleles
• Mutatnts are vulvaless and multivulva
Equivalence group – made up of 6 P3p-P8p cells, which are
all competent to make vulva and replace each other in various
experimental situations
Anchor cell – lies internally adjacent to P6p which shows
evidence of the equivalence group
Laser microbeam radiation – method in which anchor cell
is ablated and all P3p-P8p cells follow the 3° fate and no vulva
is produced
Removal of 1 P3p-P8p cells – in certain cases, 1 of the
neighbors will take its place and a normal vulva will be
produced
Displaced gonadal mutants – occurs whenever an anchor
cell is moved relative to the P3p-P8p cells, whichever is the
nearest will produce the vulva
Vulvaless mutants:
Homolog Encoded by
Anchor cell ligand EGF lin-3
Receptor EGF receptor let-23
Vertebrate Ras --- let-60
let-60
• loss-of-function - has opposite phenotypes
• gain-of-function – gives a multivulva phenotype
• double mutant combinations – works in
predictable ways
o e.g. let-23 + let-60 gof = multivulva
phenotype
Gradient of EGF – enough to generate the 3 cell fates
P6p – emits 2° signal that activates Notch pathway in P5p and P7p
C. THE GERMLINE
• Derives from P4 cell – inherits various determinants
(associated with P-granules)
• PIE-1 protein – repress genes transcribed by RNA
polymerase II during early stages
• Newly hatched larva:
Consists of 2 cells descended from P4 cell: Z2 and Z3
- Express cgh-1 gene (encodes and RNA helicase)
*homologous to vasa in Drosophila.
- CGH-1 protein is one of the components of P-
granules
• Larval and adult worm – germ cells lie within the gonad
- 60 L2 stage, 2000 adult hermaphrodite
• Initially mitotic, meiotic zone appears
• Produces sperm, later switches to oocyte production
• Mostly translation rather than transcription control
• Most mature cells lie on the vulva; most immature cells
(still mitotic) at blind ends of gonad
• Do not form a true syncytium
• DISTAL TIP CELL (DTC) – somatic cell at tip of each
branch of the gonad
- Maintain the neighboring germ cell nuclei in mitosis
- Two cells derive from Z1 and Z4 *progeny of MS
blastomere
> Experience a high ratio of SYS-1 to POP-1,
and became distal tip cells
> Proximal daughters with low and repressive
POP-1, form anchor cells that control formation of vulva
- Specified by the same WnT-like mechanism
- Acts by expression of lag-2 (homolog of delta)
- glp-1 encoded a receptor that is present on the
germ-cell syncytial membrane.
- Zygotic loss-of-function mutations of glp-1 or lag-2
= same effect as ablation of the DTC
• Gonads growth during larval life, mitotic germ-cell
elongate = leaves the range of influence of the distal tip
cell (stop mitotic division) then enters meiosis.
• Laser irradiation causes all remaining mitotic nuclei to
enter meiosis
• Early ablation – create all sperm; late ablation – nearly
normal arrangement of oocytes and sperm
• GLP-1 signal inhibits the activity of a pair of proteins
➢ GLD-1 (RNA binding protein), GLD-2 (polyA
polymerase) *needed for progression to meiosis
➢ Upregulates daz-1 – required for oogenesis

! externalized by the dying cell and to transduce the signal
VI. PROGRAMMED CELL DEATH
- apoptosis
o Lose Lose contact with neighboring cells
o Condensation of the nucleus
o Shinkage of the cell to a membrane bound
body
o Engulfment
- 131 cells die out of 1090 somatic cells
- Cell-death-defective (ced) mutants
o affect all the cell deaths in the organism
o interfere with the engulfment of dead cells
Three components of actual death program:
1. ced-3 –Loss of function (excessive cell death)
2. ced-4- Loss of function (excessive cell death)
3. ced-9- Both loss of function and gain of function (some
survival of cells that normally die)
ced-9 codes BCL2 (mammalian homolog protein)
o inhibits cell death
ced-3 codes 1 β-converting enzyme(ICE)
o Cysteine protease that cleaves at Asp-X
(member of family caspases (enymes that
targets cell death
*ced-4 activates ced-3 and is inhibited by ced-9
Engulfment
!
The engulfment process is mediated by two partially
redundant pathways. In the CED-1/CED-6/CED-7
pathway, CED-1 and CED-7 act on the surface of the
engulfing cell to mediate recognition of an unknown
engulfment signal(s) on the surface of the dying cell (green
diamonds) and to transduce the signal through CED-6 to
activate the phagocytic machinery of the engulfing cell.
CED-7 also acts in dying cells. In the CED-2, CED-5,
CED-10 and CED-12 pathway, PSR-1 may act in the
engulfing cell to mediate the recognition of PS (red circles)
through the CED-2/CED-5/CED-12 ternary complex to
activate CED-10. There are likely other engulfment
receptors that act in the CED-2, CED-5, CED-10 and
CED-12 pathway
✓ “eat me” signals are rapidly exposed of the dying cell
which then recognized by engulfing cells
✓ Genetic analyses have identified eight genes:

ced-1, ced-2, ced-5, ced-6, ced-7, ced-10,
ced-12, psr-1 (phosphatidylserine receptor homologue)

which appear to function in two pathways to promote
the cell corpse engulfment process with ced-1, ced-6,
and ced-7 acting in one pathway ced-2, ced-5, ced-10,
ced-12, psr-1 in another pathway.
o ced-1 is similar to the human scavenger
receptor (SREC)
o ced-7 is similar to ABC (ATP-Binding cassette),
play a role in promoting cell corpse recognition
by ced-1
o ced-6 contains PTB(phosphatyrosube-binding)
domain which directly binds to the intacellular
domain ced-1.
-act as a signaling adaptor downstream of
ced-1 and ced-7
Reiterated