Cell-cycle kinetics of neocortical precursors are influenced by embryonic thalamic axons

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 1 4 mouse thalamic axons release a diffusable factor that promotes the prolif eration of cortical precursors over a restricted developmental window. The thalamic mitogenic effect on cortical precursors (1) shortens the total cel l-cycle duration via a reduction of the G(1) phase; (2) facilitates the G(1 )/S transition leading to an increase in proliferative divisions; (3) is si gnificantly reduced by antibodies directed against bFGF; and (4) influences the proliferation of both glial and neuronal precursors and does not precl ude the action of signals that induce differentiation in these two lineages . We have related these in vitro findings to the in vivo condition: the org anotypic culture of cortical explants in which anatomical thalamocortical i nnervation is preserved shows significantly increased proliferation rates c ompared with cortical explants devoid of subcortical afferents. These resul ts are in line with a number of studies at subcortical levels showing the c ontrol of neurogenesis via afferent fibers in both vertebrates and inverteb rates. Specifically, they indicate the mechanisms whereby embryonic thalami c afferents contribute to the known early regionalization of the ventricula r zone, which plays a major role in the specification of neocortical areas.