John Mains-Sheard

One of the unsolved mysteries in evolutionary development is how organ size is controlled, and the vertebrate limb is a powerful model to investigate how diffusible factors emanating from the flank and distal epithelium interact with genetically-controlled ‘tempo’. I propose to use complementation of limbless blastocysts to generate rat-to-mouse chimeras in which either the hindlimb mesenchyme or the hindlimb epithelium is of rat origin, while remaining tissues stem from the mouse host. I expect to identify gene regulatory networks differentially active between normal rat-limb cells and chimeric-limb cells. This knowledge would further our understanding of evolution and allow manipulation of organ size.