[S6.5]: Sox proteins in glial fate and development

Our studies aim to understand the regulation and function of the neural specific class of bHLH transcription factors in directing processes involved in the transition from proliferating neural stem cells to differentiating neurons and glia. Alteration in function and expression of different bHLH factors results in imbalances in excitatory and inhibitory neuron formation and loss of control of neural cell number. Ascl1 (previously Mash1) and Ptf1a are two such factors essential for the generation of inhibitory neurons in multiple regions of the nervous system including our model system, the dorsal spinal cord. Using mouse genetics and Cre-flox fate mapping strategies we find that Ascl1 is present in neuronal and glial restricted progenitor cells at different times during neural tube development. It is required in these progenitors for differentiation into specific subsets of dorsal horn neurons (dILA inhibitory interneurons) and for differentiation of oligodendrocytes. In contrast, Ptf1a is only in neuronal restricted lineages and is essential for generation of inhibitory interneurons in multiple regions. Ptf1a is unique in that it forms a novel transcription complex (PTF1J) that includes Rbpj. It is notable that Ptf1a dependent neuronal specification is occurring in the neural tube in a similar temporal window as neuronal differentiation, a process controlled by Ascl1 in balance with Notch signaling. The Notch pathway also requires a transcription complex with Rbpj. A model is suggested in which distinct transcription complexes utilize shared components to couple decisions in neuronal differentiation and specification. ChIP-Seq technology is being used to define the genome wide targets of these essential regulatory factors to uncover principles of transcriptional control during development.