[P138]: Foxg1 is required cell autonomously for dorso‐ventral patterning of the telencephalon, in part by regulating the response to hedgehog signalling

Sub-regionalization of the brain into smaller subdivisions involves local signaling centers such as the floor plate, roof plate and zona limitans intrathalamica (ZLI). While mutation of WNT3 in human results in a hereditary disease that affects the development of many organs, including the CNS, the causal effects of these events are ill understood. Using zebrafish as our animal model, we isolated the gene encoding this protein and studied its role in neural development. wnt3 is characteristically expressed in the anterior floor plate, diencephalic roof plate and ZLI. Our results from loss-of-function experiments using various molecular markers and in vivo imaging of enhancer-trap GFP transgenic lines showed that Wnt3 is required for the development of dorsal diencephalon, in particular habenula and dorsal thalamus. Cells in these regions were unable to differentiate in the absence of Wnt3. Conversely, over-expression experiments using in vivo electroporation of DNA (Teh et al., 2003) demonstrated that brain-specific over-expression of Wnt3 increased cell differentiation in the dorsal brain. We further showed that the signalling mechanism involved up-regulation of -catenin. Finally, neuronal differentiation defect observed in Wnt3 morphants can be rescued by targeted electroporation of Wnt3. Together these results demonstrate influence of Wnt3 on neuronal differentiation in dorsal diencephalon, a region involved in relaying ascending sensory information to the telencephalon as well as regulation of cyclic behaviour, such as the circadian rhythm and reproductive cycles.