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The bHLH Nex-1 transcription factor induces GAP-43 expression and promotes neuronal differentiation

The bHLH Nex-1 transcription factor induces GAP-43 expression and promotes neuronal differentiation

Society for Neuroscience Abstracts 26(1-2): Abstract No -600 15

The Nex-1 gene encodes a neuronal-specific transcription factor belonging to the basic Helix-Loop-Helix (bHLH) family. Nex-1 expression is restricted to post-mitotic neurons during brain development. Its expression parallels overt neuronal differentiation and synaptogenesis. Our objective has been to elucidate the transcriptional pathways controlled by Nex-1 during neuronal differentiation. We previously demonstrated that Nex-1 activates the GAP-43 promoter through the E1-E2 E-boxes. Here, we show that Nex-1 stimulates the endogenous expression of GAP-43 in PC12 cells and that overexpression of Nex-1 in PC12 cells induces neurite outgrowth in absence of NGF. Furthermore, we found that overexpressing Nex-1 increases NGF effect on neurite outgrowth and neurite regeneration. To unravel the molecular mechanisms of action of Nex-1, we addressed the question whether Nex-1 targets additional neuronal-specific genes. Our preliminary results indicate that Nex-1 modulates the expression of several structural and functional genes. In summary, our results suggest that Nex-1 may be a functional component of the NGF pathway in PC12 cells.

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