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First published online 3 May 2006
doi: 10.1242/dev.02377

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The GATA2 transcription factor negatively regulates the proliferation of neuronal progenitors

Abeer El Wakil^*, Cédric Francius^*,, Annie Wolff, Jocelyne Pleau-Varet and Jeannette Nardelli^,

UMR CNRS 7000, Cytosquelette et Développement, Faculté de Médecine Pitié-Salpêtrière, 105 boulevard de l'Hôpital, 75013 Paris, France and Université Pierre et Marie Curie, Paris 6, France.

Author for correspondence (e-mail: nardelli{at}ext.jussieu.fr)

Accepted 27 March 2006

Postmitotic neurons are produced from a pool of cycling progenitors in an orderly fashion that requires proper spatial and temporal coordination of proliferation, fate determination, differentiation and morphogenesis. This probably relies on complex interplay between mechanisms that control cell cycle, specification and differentiation. In this respect, we have studied the possible implication of GATA2, a transcription factor that is involved in several neuronal specification pathways, in the control of the proliferation of neural progenitors in the embryonic spinal cord. Using gain- and loss-of-function manipulations, we have shown that Gata2 can drive neural progenitors out of the cycle and, to some extent, into differentiation. This correlates with the control of cyclin D1 transcription and of the expression of the p27/Kip1 protein. Interestingly, this functional aspect is not only associated with silencing of the Notch pathway but also appears to be independent of proneural function. Consistently, GATA2 also controls the proliferation capacity of mouse embryonic neuroepithelial cells in culture. Indeed, Gata2 inactivation enhances the proliferation rate in these cells. By contrast, GATA2 overexpression is sufficient to force such cells and neuroblastoma cells to stop dividing but not to drive either type of cell into differentiation. Furthermore, a non-cell autonomous effect of Gata2 expression was observed in vivo as well as in vitro. Hence, our data have provided evidence for the ability of Gata2 to inhibit the proliferation of neural progenitors, and they further suggest that, in this regard, Gata2 can operate independently of neuronal differentiation.

Key words: GATA2, Cell cycle, Neuronal progenitors, Posterior neural tube, Mouse, Chick

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