Anton E S, Cameron R S, Rakic P
Section of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510-8001, USA.
J Neurosci. 1996 Apr 1;16(7):2283-93. doi: 10.1523/JNEUROSCI.16-07-02283.1996.
To identify glial membrane proteins that contribute to the process of neuronal migration in the developing brain, we developed a polyclonal antiserum (D4) and a monoclonal antibody (NJPA1: neuron-glial junctional polypeptide antibody) that recognize membrane proteins localized to the plasmalemmal junction between migrating neurons and adjacent radial glial fibers (Cameron and Rakic, 1994). Here, we show that in the developing cerebral cortex, immunoreactivity for these junctional polypeptides is present throughout the neuronal migratory pathway but becomes minimal or absent where radial glial cell processes enter the marginal zone region, the barrier at which newly arrived neurons normally stop their migration and detach from their glial fiber substrate. We thus tested, using imprints of embryonic cerebral wall and slice preparations, whether the junctional membrane proteins detected by our antibodies contribute to the regulation of neuronal migration in the cerebral cortex. The rate of neuronal migration on glial cell substrates was reduced significantly in the presence of D4 or NJPA1 antibodies. Antibody exposure typically led to the withdrawal of leading processes, changes in microtubular organization and, in some instances, to detachment of neurons from their glial cell substrates. These results suggest that the polypeptides recognized by the D4 and NJPA1 antibodies are essential for the maintenance of normal neuronal migration. Dismantling of neuron-glial cell junctional domains formed by these membrane proteins may underlie neuronal cell detachment from glial migratory substrates at the interface between cortical plate and marginal zone in the developing cerebral wall.
为了鉴定在发育中的大脑中对神经元迁移过程有贡献的胶质细胞膜蛋白，我们制备了一种多克隆抗血清（D4）和一种单克隆抗体（NJPA1：神经元 - 胶质细胞连接多肽抗体），它们可识别定位于迁移神经元与相邻放射状胶质纤维之间质膜连接处的膜蛋白（Cameron和Rakic，1994年）。在此，我们表明，在发育中的大脑皮层中，这些连接多肽的免疫反应性在整个神经元迁移途径中都存在，但在放射状胶质细胞突起进入边缘区区域（新到达的神经元通常在此处停止迁移并与它们的胶质纤维底物分离的屏障）时变得极少或不存在。因此，我们使用胚胎脑壁印记和切片标本进行测试，以确定我们抗体检测到的连接膜蛋白是否有助于调节大脑皮层中的神经元迁移。在存在D4或NJPA1抗体的情况下，神经元在胶质细胞底物上的迁移速率显著降低。抗体暴露通常导致前端突起缩回、微管组织变化，并且在某些情况下，导致神经元与它们的胶质细胞底物分离。这些结果表明，D4和NJPA1抗体识别的多肽对于维持正常的神经元迁移至关重要。由这些膜蛋白形成的神经元 - 胶质细胞连接结构域的解体可能是发育中的脑壁中皮质板和边缘区界面处神经元从胶质迁移底物上脱离的基础。
