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Journal of Cell Science, Vol 113, Issue 15 2705-2713, Copyright © 2000 by Company of Biologists

JOURNAL ARTICLES

Goosecoid suppresses cell growth and enhances neuronal differentiation of PC12 cells

K Sawada, Y Konishi, M Tominaga, Y Watanabe, J Hirano, S Inoue, R Kageyama, M Blum and A Tominaga
Department of Neuropsychiatry, Kochi Medical School, Kohasu, Okoh-cho, Nankoku City, Kochi 783-8505, Japan.

In all vertebrate species, the homeobox gene goosecoid serves as a marker of the Spemann organizer tissue. One function of the organizer is the induction of neural tissue. To investigate the role of goosecoid in neuronal differentiation of mammalian cells, we have introduced goosecoid into PC12 cells. Expression of goosecoid resulted in reduced cell proliferation and enhanced neurite outgrowth in response to NGF. Expression of goosecoid led to a decrease in the percentage of S-phase cells and to upregulation of the expression of the neuron-specific markers MAP-1b and neurofilament-L. Analysis of goosecoid mutants revealed that these effects were independent of either DNA binding or homodimerization of Goosecoid. Coexpression of the N-terminal portion of the ets transcription factor PU.1, a protein that can bind to Goosecoid, repressed neurite outgrowth and rescued the proliferation of PC12 cultures. In contrast, expression of the bHLH transcription factor HES-1 repressed goosecoid-mediated neurite outgrowth without changing the proportion of S-phase cells. These results suggest that goosecoid is involved in neuronal differentiation in two ways, by slowing the cell cycle and stimulating neurite outgrowth, and that these two events are separately regulated.


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