Shankar Srinivas

Embryogenesis is the process by which a fertilized egg, consisting of a single apparently amorphous cell, develops into the final adult form, composed of many cells arranged in structures with specific shapes.  If this process is perturbed, it can lead to congenital abnormalities.

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.

Current Research Programme

We use a combination of basic embryology, molecular genetics and time-lapse microscopy to:

• Clarify the cellular mechanism for anterior patterning in mouse embryos, specifically with respect to the stereotypic migration of cells of the Anterior Visceral Endoderm, which is responsible for proper anterior specification of the embryo.  We do this not only in the context of cultured wild type and mutant embryos, but also in vitro, to study how extra-cellular matrix proteins and other factors might be responsible for guiding the migration of AVE cells.
• Create a novel genetic fate map of cells in various gene expression domains of the early embryo.  We do this by using fluorescent reporter strains of mice that express the reporter only upon induction by Cre recombinase.  By using gene regulatory elements to drive tissue specific expression of inducible forms of Cre, we can label specific populations of cells and follow their fate by time-lapse microscopy.

Both these approaches ultimately aim to clarify the dynamic processes underlying embryonic patterning.