Cells lacking N-CoR form astroglia (bottom) but not neurons (top).

Rosenfeld/Macmillan

The discovery of MyoD was stunning: it suggested that a few critical activators might determine the differentiated states of tissues such as, in this case, muscle. Now Ola Hermanson, Kristen Jepsen, and Michael Rosenfeld (University of California, San Diego, CA) have found that the undifferentiated state also has critical determinants. This time, however, the determinant is called N-CoR, and it is a corepressor.

Hermanson and colleagues found that mice lacking N-CoR had a decrease in the size of certain brain regions, and cells cultured from the mice had lost the ability to self-renew. Instead, the cells differentiated, in the absence of the normal differentiating signals, into something resembling astroglia. The cells were not responsive to signals favoring neuronal differentiation.

CNTF induces differentiation of normal neural precursors into astroglia. The authors found that this involved Akt-mediated phosphorylation of N-CoR. Phosphorylated N-CoR translocated out of the nucleus, and thus could no longer act as a corepressor for several transcription factors.

N-CoR is active in tissues other than the brain. But, says Rosenfeld, “it would be totally naïve to consider that the absence of N-CoR is all it takes to differentiate.” He does believe, however, that the N-CoR results demonstrate a larger principle. “You need a dedicated apparatus to maintain a proliferative or dedifferentiated state, often involving repressors,” he says. “I think there is a huge cohort of repressors mediating this, probably as many as there are activators for differentiation.” ▪

Reference:

Hermanson, O., et al. 2002. Nature. 10.1038/nature01156.