Beruflich Dokumente
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Lecture Outline
Introductory Notes
The Timing of Gastrulation and Subsequent Events
Formation of the Epiblast & Hypoblast
Role of Gastrulation
Human Gastrulation: How Do We Know How it Works?
Gastrulation in Human Embryo
Cell Movements & Rearrangements during Embryonic Development
Cross Section of Human Gastrula
Bottle Cells: Epithelial-Mesenchymal Transformation
Early Cell Lineages in the Human Embryo
Mammalian Pattern & Polarity
Left-Right Axis Determination
Do Nodal Cilia Define Symmetry?
References
Introductory Notes
Delamination precedes gastrulation separating ICM into epiblast & hypoblast
Gastrulation occurs in epiblast (future embryo)
Gastrulation involves several types of movements, shape changes and oriented cell divisions
End product is three germ layers: ectoderm, endoderm and mesoderm
The gene expression will regulate the formation of the embryonic axes & the organization of the embryo
The Timing of Gastrulation and Subsequent Events
Gastrulation begins about 15 days of development and is followed by neurulation and the start of
development of several major organ systems as shown in the following figure
Historically, mark embryos with particles & dyes to follow cell movements
More Recently: Researchers have fluorescently labeled cells & followed their movement by confocal
microscopy (a special laser-based microscopy which allows you to take optical sections through tissues to
construct 3-D images) and obtain sharper resolution of stained material and its location.
The node was discovered in mammals by Hensen and is appropriately named Hensen's node in rabbits and
other organisms but is only referred to as the primitive node or simply node in humans.
The cells that enter through the primitive node will become the notochord (see lecture on neurulation).
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Ingression: cells break away from the tissue and migrate as individuals (epithelial-mesenchymal transition
during human gastrulation)
Delamination: layers of cells separate from each others more or less as sheets of cells (formation of the
epiblast/hypoblast)
Intercalation: two cell layers interlace with each other
Epiboly: a form of cell spreading in which cells flatten out; this allows them to cover a much larger surface
area (1st detailed in frog development); surface of epiblast during gastrulation.
Invagination (Evagination): a tissue layer folds in (out); optic (eye) vesicle formation
Involution: cells move over a lip of tissue and into the interior
Convergent Extension: cells reorganize to form less layers allowing the cells to extend out from a point;
formation of the chordamesoderm (notochordal process).
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After Figure 3-2 from Larsens Human Embryology. Genes involved in establishing left-right symmetry.
Initially Shh is expressed uniformly in the primitive node but over time it becomes expressed predominantly
on the left side. This is followed by the increased expression of Nodal (a transforming growth factor beta,
TGF, family member) on the left side of the primitive node. In turn, this is followed by the expression of
another TGF, family member Lefty2. Finally the transcription factor Pitx2 is activated which presumably
regulates a number of genes some of which are involved in lateral plate mesoderm differentiation. Other
factors such as fibroblast growth factor 8 (Fgf8) plus Lrd and Kif which are mentioned below are also
involved.
Do Nodal Cilia Define Symmetry?
The cell communication events mediating the development of the left axis are under analysis. Shh is a
diffusible molecule that regulates signaling events in other cells. The nodal flow model suggests that
morphogens and signaling molecules involved in defining the left-right axes is driven by the action of cilia
that cause molecules to flow from right to left across the primitive node (see arrow in above diagram). In
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Figure 3-4 from Larsens Human Embryology. A. SEM of monociliated cells in mouse node. B. Nodal flow model involving
NVPs and calcium ions.
There are interpretations of the nodal flow model. One is that the cilia flow directs soluble morphogens and
factors from right to left. While others suggest the Nodular Vesicular Particles (NVPs) are released from
right cells and carried to those on the left by ciliary action. Either of these or even other events lead to higher
calcium ion levels on the left which could direct left-side cell fate decisions. The nodal flow model gets
support from the fact that mutations in ciliary dynein can lead to sinus inversus (i.e., right-left switching) for
various organs (e.g., heart as seen in Kartageners syndrome).
References
Tam et al, 2006. Building the mouse gastrula: signals, asymmetry and lineages. Current Opinion in Genetics
& Development 16: 419-425.
Copyright 1998-2010 Danton H. O'Day
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