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Main Goal
Our main focus is to understand the signals
necessary for patterning and specifying diverse
cellular fates during gastrulation in the mouse.
Mouse gastrulation, even more so than amphibian and
teleost gastrulation, is a period of vast
differentiation and growth. During this stage, the
mouse embryo transitions from having only two cell
types to having hundreds. Although an incredibly
rich source of cell signaling, the mouse gastrula
has not been used by molecular biologists to mine
for molecules. This is mainly due to the size (100
µm) and inaccessibility of the mouse gastrula, which
therefore precludes the effective use of
biochemistry, embryology and molecular assays in
general.
Approach
We have devised a screen that identifies molecules
involved in cell-fate specification during mouse
gastrulation. This approach delivers random
combinations of cDNAs from mouse gastrula libraries
into the more tractable Xenopus embryo. We then
observe these embryos for changes in specific marker
gene expression, indicating changes (positive or
negative) in cell-fate. We are particularly
interested in the alteration of mesodermal,
endodermal, neural, endothelial and somitic
cell-fate decisions. Using this screen we have
identified over 40 molecules, several of which have
no previously understood function. |
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