Foxg1-dependent regulatory network controlling telencephalic boundary and neuronal fate specification. (360G-Wellcome-091796_Z_10_Z)

Telencephalic neuronal cell fates are dependent upon reception of secreted signals that establish graded expression of transcription factors such as Foxg1. However, the mechanism by which these are controlling cell type decisions is still elusive. We recently found that Foxg1 is a central integrator of two key signaling centres, and drew a coherent model of the genetic interactions controlling subpallial/pallial patterning in vertebrates. Identifying the mechanisms by which Foxg1 is carrying its integrative function is key to understanding both telencephalic neuronal specification and neurologic dysfunctions found in human disorders such as the congenital form of Rett syndrome. This proposal aims to dissect the molecular mechanisms by which Foxg1 controls subpallial/pallial fate specification. The specific questions addressed here are: - Are Eph/Ephrins targets of Foxg1, acting upon both boundary formation and neurogenesis? - Is the mechanism by which Foxg1 drives telencephalic f ates Gli-dependent? - Are discreet levels of Foxg1 activity driving distinct telencephalic fates? - What are Foxg1 partners and targets involved in DV fate specification and boundary formation? High throughput technologies will be used to identify Foxg1 partners (in vivo cross-linking and large scale mass spectrometry) and targets (ChIP-Seq). The experimental models chosen are zebrafish and mouse.