Neurogenin Actively Inhibits Astrogenesis

Science's STKE  13 Feb 2001:
Vol. 2001, Issue 69, pp. tw3
DOI: 10.1126/stke.2001.69.tw3

Neurogenin is a basic loop-helix-loop transcription factor involved in promoting neural differentiation by increasing the expression of neuronal genes. Glial differentiation is known to proceed from the activation of the Jak/STAT pathway downstream of the cytokines LIF and CNTF and from activation of a Smad pathway downstream of bone morphogenic protein (BMP). Sun et al. show that neurogenin also actively inhibits glial differentiation by mechanisms that do not require DNA binding by neurogenin. One mechanism for this repression of glial differentiation arises by neurogenin's ability to interact with the transcription coactivator CBP/p300 and the transcription factor Smad1, preventing the formation of the CBP/p300-Smad1-STAT3 complex required for the induction of glial specific genes. Overexpression of neurogenin in neural stem cell cultures suppresses phosphorylation of STAT1 and STAT3 in response to LIF and CNTF. Thus, neurogenin is a transcriptional activator as a transcription factor for neurogenesis and a signal transduction inhibitor with regard to glial differentiation.

Y. Sun, M. Nadal-Vicens, S. Misono, M. Z. Lin, A. Zubiaga, Z. Hua, G. Fan, M. E. Greenberg, Neurogenin promotes neurogenesis and inhibits glial differentiation by independent mechanisms. Cell 104, 365-376 (2001). [Online Journal]