Dehay C, Savatier P, Cortay V, Kennedy H
Institut National de la Santé et de la Recherche Médicale U371, Cerveau et Vision, 69500 Bron, France.
J Neurosci. 2001 Jan 1;21(1):201-14. doi: 10.1523/JNEUROSCI.21-01-00201.2001.
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 G(1) phase; (2) facilitates the G(1)/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.
已知丘脑传入纤维在发育后期对皮质区域的分化发挥控制作用。在此，我们表明丘脑传入纤维在脑室区水平也影响皮质发生的早期阶段。利用体外实验方法，我们发现胚胎第14天小鼠的丘脑轴突释放一种可扩散因子，该因子在有限的发育窗口期促进皮质前体细胞的增殖。丘脑对皮质前体细胞的促有丝分裂作用：(1) 通过缩短G1期来缩短整个细胞周期时长；(2) 促进G1/S期转换，导致增殖性分裂增加；(3) 被抗碱性成纤维细胞生长因子（bFGF）的抗体显著降低；(4) 影响神经胶质前体细胞和神经元前体细胞两者的增殖，并且不排除诱导这两个谱系分化的信号的作用。我们已将这些体外实验结果与体内情况联系起来：保留丘脑皮质神经支配解剖结构的皮质外植体的器官型培养物，与缺乏皮质下传入纤维的皮质外植体相比，显示出显著提高的增殖率。这些结果与一些在皮质下水平的研究一致，这些研究表明在脊椎动物和无脊椎动物中，通过传入纤维对神经发生进行控制。具体而言，它们指出了胚胎丘脑传入纤维促成脑室区已知早期区域化的机制，脑室区在新皮质区域的特化中起主要作用。
