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Neurogenin Inhibits Astrogenesis

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Science  02 Mar 2001:
Vol. 291, Issue 5509, pp. 1667
DOI: 10.1126/science.291.5509.1667c

In generating neurons and glia from neural stem cells developmental choices must be made. Neurogenin is a transcription factor involved in promoting neuronal differentiation by increasing the expression of neuronal genes. Glial differentiation results from the activation of the Jak/STAT pathway downstream of two cytokines, LIF and CNTF, and from activation of a Smad pathway downstream of bone morphogenic protein.

Now Sun et al. show that neurogenin also actively inhibits glial differentiation by mechanisms that do not require it to bind DNA. Instead, neurogenin interacts with the transcription coactivator CBP/p300 and the transcription factor Smad1 to prevent the formation of a CBP/p300-Smad1-STAT3 complex required for the induction of glial-specific genes. Overexpression of neurogenin in neural stem cell cultures suppressed phosphorylation of STAT1 and STAT3 in response to LIF and CNTF. Thus, neurogenin acts independently as a transcriptional activator for neurogenesis and as a signal transduction inhibitor in glial differentiation. — JN

Cell104, 365 (2001).

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