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Gastrulation through a primitive streak - cellular mechanics and signals

Reference	BB/C512753/1
Principal Investigator / Supervisor	Professor Claudio Stern
Co-Investigators / Co-Supervisors
Institution	University College London
Department	Cell and Developmental Biology
Funding type	Research
Value (£)	262,982
Status	Completed
Type	Research Grant
Start date	19/03/2005
End date	18/03/2008
Duration	36 months

Abstract

Gastrulation is the period in embryonic development when the three main germ layers (ectoderm, mesoderm and endoderm) are laid down, and when the polarity of the embryo first becomes irreversibly fixed. As such, it is one of the most important events in the development of the embryo. However, almost everything we know about how cells ingress from the epiblast to form the definitive layers is based on studies in Echinoderms (sea urchin) and amphibians (Xenopus and newts), which gastrulate through a blastopore. In the sea urchin, gastrulation begins by ingression of individual primary mesenchyme cells which accumulate vegetally and then induce other superficial cells to undergo massive ingression to form the blastopore, a process that involves signalling by the Notch pathway. Likewise, in Xenopus, deep cells are present prior to the formation of a visible blastopore. Higher vertebrate embryos do not have a blastopore but rather a primitive streak. Here we will address the following questions: How does ingression occur through a primitive streak? How is it regulated? Do amniote embryos have a primary mesenchyme, and do these cells induce others to form a primitive streak? What are the signals mediating this interaction: is Notch involved? How do cells regulate their gene expression profile during their movement? We will use chick embryos which are large and flat and translucent yet very similar to non-rodent mammals, and a draft sequence of the entire genome has recently been completed. We will combine detailed morphological analysis by conventional scanning electron microscopy and plastic sections of embryos stained by whole-mount in situ hybridisation as well as classical transplantation experiments, with more recently developed technology including 2-photon time-lapse microscopy of living embryos transfected with GFP to make 4-d films, electroporation of reporter constructs to visualise when and where the expression of specific genes is turned on and off during cellmovements, and electroporation of constructs that affect Notch signalling to determine whether this pathway is involved in primitive streak induction and or cell ingression. Finally we will endeavour to develop mathematical models to explain the mechanisms that ensure the formation of a single primitive streak and regulate its size. Taken together these studies should provide the first comprehensive view of how gastrulation is initiated in embryos with a primitive streak, rather than a blastopore.

Summary

unavailable

Committee	Closed Committee - Genes & Developmental Biology (GDB)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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