Epithelial to mesenchymal plasticity in the ventral forebrain

How, when and where are cells specified to different fates during embryogenesis to form functional organs? Specification of the neural tuberal hypothalamus has long been thought to occur through a patterning mechanism, mediated by graded morphogen signals. Furthermore, tuberal hypothalamic cells are classically thought to be distinct in lineage from endoderm. Our work challenges these ideas. Previously we showed that tuberal specification is linked to growth, tuberal cells generated as a wave of BMP signalling sweeps through hypothalamic floor plate-like (HypFP) cells. Pilot studies, including scRNA-seq studies, multiplex HCR, fate-mapping and analyses of cell behaviours in static images, indicate that HypFP cells may contribute cells to the tuberal progenitor region, Rathke’s pouch and the foregut. Here we will take a multi-pronged in vivo and ex vivo approach in the chick embryo, including clonal lineage analysis, live-imaging, and functional studies to ask: Do HypFP cells demonstrate epithelial-to-mesenchymal plasticity, enabling them/their descendants to migrate? How do candidate molecules - in particular those in a TGFβ signalling network - direct HypFP/downstream progenitor programmes, influence their epithelial characteristics and support alternate fates? When and where are distinct fates specified in HypFP-derived cells?