Li W, Cogswell C A, LoTurco J J
Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269-4156, USA.
J Neurosci. 1998 Nov 1;18(21):8853-62. doi: 10.1523/JNEUROSCI.18-21-08853.1998.
Neocortical neurons begin to differentiate soon after they are generated by mitoses at the surface of the ventricular zone (VZ). We provide evidence here that bone morphogenetic protein (BMP) triggers neuronal differentiation of neocortical precursors within the VZ. In cultures of dissociated neocortical neuroepithelial cells, BMPs increase the number of MAP-2- and TUJ1-positive cells within 24 hr of treatment. In explant cultures, BMP-4 treatment leads to an increase in the number of TUJ1-positive cells within the ventricular zone. Furthermore, truncated, dominant-negative, BMP type I receptor, introduced into neocortical precursors by retrovirus-mediated gene transfer, blocks neurite elaboration and migration out of the VZ. Finally, immunocytochemistry indicates that BMP protein is present at the VZ surface. Together, these results indicate that BMP protein is present within the VZ, that BMP is capable of promoting neuronal differentiation, and that signaling through BMP receptors triggers neuronal precursors to differentiate and migrate out of the VZ.
新皮质神经元在脑室区(VZ)表面通过有丝分裂产生后不久便开始分化。我们在此提供证据表明,骨形态发生蛋白(BMP)触发VZ内新皮质前体细胞的神经元分化。在解离的新皮质神经上皮细胞培养物中,BMP在处理24小时内增加了MAP-2和TUJ1阳性细胞的数量。在植块培养中,BMP-4处理导致脑室区内TUJ1阳性细胞数量增加。此外,通过逆转录病毒介导的基因转移引入新皮质前体细胞的截短的、显性负性的BMP I型受体,会阻断神经突的形成以及从VZ迁出。最后,免疫细胞化学表明BMP蛋白存在于VZ表面。这些结果共同表明,BMP蛋白存在于VZ内,BMP能够促进神经元分化,并且通过BMP受体的信号传导触发神经元前体细胞分化并从VZ迁出。