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Structure/function analysis of the basic helix loop helix domain of mash1 and math1 transcription factors


, : Structure/function analysis of the basic helix loop helix domain of mash1 and math1 transcription factors. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 26 3

Despite the conserved sequence in their basic-helix-loop-helix (bHLH) domains, many members of the bHLH family of transcription factors are involved in distinct developmental processes including neurogenesis, myogenesis and hematopoiesis. In order to identify functional domains in the neural bHLH proteins required for inducing neurogenesis as well as inducing specific neuronal sub-types, we focused on bHLH domains of Mash1 and Math1. For structure/function analysis, chimeric proteins, which combined different domains of Mash1 with either the muscle specific bHLH MyoD, or the neural bHLH Math1, were introduced into developing chick neural tubes by in ovo electroporation. As a result of this study, we found that helix1 of the Mash1 HLH domain is necessary for Mash1's ability to promote neurogenesis in the developing chick neural tube. Furthermore, Mash1 helix1 is sufficient to confer this function to a non-neural bHLH factor, demonstrated by replacing helix1 of MyoD with helix1 of Mash1. In contrast, helix2 is the domain responsible for the ability of Math1 and Mash1 to induce a specific sub-type of neuron in these assays. Taken together, we demonstrate that the functional domains for driving neurogenesis and neuronal cell-type specification are encoded in different domains within the HLH motif of these proteins.

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