Jossin Yves
Division of Basic Sciences; Fred Hutchinson Cancer Research Center; Seattle, WA USA; Institute of Neuroscience; University of Louvain Medical School; Brussels, Belgium.
Small GTPases. 2011 Nov 1;2(6):322-328. doi: 10.4161/sgtp.18283.
Neuronal migration is essential for the development of the cerebral cortex. Mutations leading to defective migration are associated with numerous brain pathologies. An important challenge in the field is to understand the intrinsic and extrinsic mechanisms that regulate neuronal migration during normal development and in disease. Many small GTPases are expressed in the central nervous system during embryonic development. Recent findings have shown that Rap1 and its downstream partners Ral, Rac and Cdc42 are involved in the maintenance of N-Cadherin at the plasma membrane which is necessary for the correct polarization of migrating neurons. The activation of Rap1 is triggered by Reelin, an extracellular protein known for its role in the organization of the cortex into layers of neurons. In the absence of Reelin, neurons exhibit a broader and irregular pattern of positioning. The prevailing model suggests that Reelin signals to neurons during the last step of their migration, a notion that is inconsistent with new data describing an effect of Reelin on early steps of migration. In regard to these recent findings I suggest a revised model, which I call the "polarity model," that further refines our understanding of the developmental function played by Reelin and its downstream small GTPases.
神经元迁移对于大脑皮质的发育至关重要。导致迁移缺陷的突变与众多脑部病变相关。该领域的一个重要挑战是了解在正常发育和疾病过程中调节神经元迁移的内在和外在机制。许多小GTP酶在胚胎发育期间于中枢神经系统中表达。最近的研究结果表明，Rap1及其下游伙伴Ral、Rac和Cdc42参与了N-钙黏蛋白在质膜上的维持，这对于迁移神经元的正确极化是必需的。Rap1的激活由Reelin触发，Reelin是一种细胞外蛋白，因其在将皮质组织成神经元层中的作用而闻名。在没有Reelin的情况下，神经元表现出更广泛且不规则的定位模式。普遍的模型表明，Reelin在神经元迁移的最后一步向神经元发出信号，这一观点与描述Reelin对迁移早期步骤影响的新数据不一致。关于这些最新发现，我提出了一个修订模型，我称之为“极性模型”，该模型进一步完善了我们对Reelin及其下游小GTP酶所发挥的发育功能的理解。
