The role of Notch signalling in stem cell fate choice in the embryo

Analysis of Primitive Streak stem cells and the role of Notch in their axial mesoderm derivatives

The broad interest of the laboratory aims to further our understanding of how several genetic interactions come into play at the earliest stages of development to build the developing embryo. Primitive streak formation is reputed as being `the most important time in ones life' since it generates the three germ layers of the embryo proper. The progenitor cells of these three germ layers ingress into the primitive streak where they form a resident population of stem cells for each tissue type. One main focus of the laboratory will be to gain a deeper understanding of the mechanism of regulation of these stem cells both in the mouse and the chick system. We aim to investigate the function of potential candidate signalling pathways involved in maintaining this stem cell state and in directing cell fate choice within these progenitor pools.

The laboratory has been focussing on the role of the Notch signalling pathway in the development of primitive streak derived axial tissues; namely the ventral neural tube and the underlying axial mesoderm. These tissues are believed to share a common precursor in the primitive streak. We have recently shown that in the developing chick embryo, Notch directs these primitive streak progenitors to contribute to the ventral neural tube at the expense of the axial mesoderm.

We aim to investigate which pathways Notch interacts with to bring about this cell fate choice. We also wish to investigate the level of conservation of this role for Notch. Since Notch signalling components are expressed in many stem like progenitor pools in the primitive streak we also wish to investigate the potential role of Notch signalling during cell fate specification of other progenitor cells in the streak.