A contribution to the refurbishment of laboratory space at the Sir William Dunn School of Pathology for Prof Robertson to facilitate her move from the WT Centre for Human Genetics. (360G-Wellcome-059312_Z_06_Z)

We are studying the complex cellular interactions underlying early mammalian development, and in particular the signals provided by members of the TGFß superfamily of secreted growth factors. We have previously shown that nodal activity is required for primitive streak formation and anterior patterning during gastrulation, and at later stages for establishment of the L/R body axis. We also described an essential function contributed by the Smad2 protein, the intracellular effector downstream of TGFß/activin receptors. The proposed experiments studies further dissect nodal contribution(s) during morphogenesis of the mouse organiser and establishment of the L/R body axis. We will use gene targeting techniques to selectively delete enhancer sequences controlling asymmetric and node specific nodal expression domains respectively. Using a novel in vivo cell marking system we plan to describe mesodermal subpopulations derived from the node and its progenitors. We will also test the role of the Smad2 pathway during node morphogenesis. Overall the proposed experiments should provide a clearer understanding of TGFß signalling pathways during mouse development.