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Patterning and morphogenesis of the early mammalian embryo

Early mouse embryos showing anterior visceral endoderm (AVE) in green. Left: still from time-lapse recording of migrating AVE cells. Middle: fixed embryo labeled for f-actin (red) and nucleii (blue). Right: higher magnification view of stained embryo showing columnar nature of cells. S. Srinivas
Early mouse embryos showing anterior visceral endoderm (AVE) in green. Left: still from time-lapse recording of migrating AVE cells. Middle: fixed embryo labeled for f-actin (red) and nucleii (blue). Right: higher magnification view of stained embryo showing columnar nature of cells.

Embryonic development is the process by which the fertilized egg, a single apparently amorphous cell, develops into the final adult form composed of many cells arranged in structures with specific shapes. It does not consist simply of the growth in size of a preformed ‘homunculus’ but is tremendously dynamic, characterised by large scale cell movement and tissue remodelling. This process has to be carefully choreographed so that morphogenesis takes place correctly and reproducibly.

Cell movements play a central role throughout mammalian embryogenesis, for instance during gastrulation, in the formation of the germ cell lineage and during the formation of the heart. An understanding of such dynamic processes is important in integrating our increasingly detailed knowledge of molecular and genetic regulatory networks into the context of cellular interactions during embryogenesis. The movement of cells during development is also intimately connected to their ultimate fate. Knowing the normal fate of cells is important not only for an understanding of development, but also has implications for therapy in humans, as it relates to the developmental potential of embryonic cells that may represent populations of stem cells.

Our group works on how cell movement is controlled during mouse embryogenesis, particularly focusing on the following problems:

  • the cellular mechanism for anterior patterning in mouse embryos, specifically with respect to the stereotypic migration of cells of the Anterior Visceral Endoderm (AVE), which is responsible for proper anterior specification of the embryo. AVE cells move within the context of an intact simple epithelial sheet and provide a good model for the study of directed epithelial cell movements.
  • how the molecular motors that cause cell movements work in a coordinated manner to bring about stereotypic cellular and tissue behaviour. We do this by perturbing and visualizing  F-actin function and dynamics in migrating epithelial cells.
  • what influence physical parameters have on cell fate specification during the formation of the pluripotent inner cell mass and its subsequent differentiation into other cell types. We do this by modulating the mechanical environment of cultured embryos to determine how this affects development and by interrogating 4D vector models of early embryonic development, produced using high-resolution time-lapse image data of developing embryos obtained using light-sheet microscopy. 

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