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The Journal of Neuroscience, January 1, 2001, 21(1):201-214
Cell-Cycle Kinetics of Neocortical Precursors Are Influenced by Embryonic Thalamic Axons
Colette Dehay1, Pierre Savatier2, Véronique Cortay1, and Henry Kennedy1 1 Institut National de la Santé et de la Recherche Médicale U371, Cerveau et Vision, 69500 Bron, France, and 2 Ecole Normale Supérieure de Lyon Laboratoire de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5665, 69364 Lyon Cedex 07, France
Thalamic afferents are known to exert a control over the differentiation of cortical areas at late stages of development. Here, we show that thalamic afferents also influence early stages of corticogenesis at the level of the ventricular zone. Using an in vitro approach, we show that embryonic day 14 mouse thalamic axons release a diffusable factor that promotes the proliferation of cortical precursors over a restricted developmental window. The thalamic mitogenic effect on cortical precursors (1) shortens the total cell-cycle duration via a reduction of the G1 phase; (2) facilitates the G1/S transition leading to an increase in proliferative divisions; (3) is significantly reduced by antibodies directed against bFGF; and (4) influences the proliferation of both glial and neuronal precursors and does not preclude the action of signals that induce differentiation in these two lineages. We have related these in vitro findings to the in vivo condition: the organotypic culture of cortical explants in which anatomical thalamocortical innervation is preserved shows significantly increased proliferation rates compared with cortical explants devoid of subcortical afferents. These results are in line with a number of studies at subcortical levels showing the control of neurogenesis via afferent fibers in both vertebrates and invertebrates. Specifically, they indicate the mechanisms whereby embryonic thalamic afferents contribute to the known early regionalization of the ventricular zone, which plays a major role in the specification of neocortical areas.
Key words: development; cortex; proliferation; areal specification; mouse; ventricular zone
Copyright © 2001 Society for Neuroscience 0270-6474/01/211201-14$05.00/0
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