Robichaux Michael A, Cowan Christopher W
Department of Psychiatry, Harvard Medical School, McLean Hospital, 115 Mill Street, Belmont, MA, 02478, USA.
Curr Top Behav Neurosci. 2014;16:19-48. doi: 10.1007/7854_2013_255.
The development of the vertebrate nervous system, including the brain and spinal cord, progresses in a step-wise fashion that involves the function of thousands of genes. The birth of new neurons (also known as neurogenesis) and their subsequent migration to appropriate locations within the developing brain mark the earliest stages of CNS development. Subsequently, these newborn neurons extend axons and dendrites to make stereotyped synaptic connections within the developing brain, which is a complex process involving cell intrinsic mechanisms that respond to specific extracellular signals. The extension and navigation of the axon to its appropriate target region in the brain and body is dependent upon many cell surface proteins that detect extracellular cues and transduce signals to the inside of the cell. In turn, intracellular signaling mechanisms orchestrate axon structural reorganization and appropriate turning toward or away from a guidance cue. Once the target region is reached, chemical synapses are formed between the axon and target cell, and again, this appears to involve cell surface proteins signaling to the inside of the neuron to stabilize and mature a synapse. Here, we describe some of the key convergent and, in some cases, divergent molecular pathways that regulate axon guidance and synaptogenesis in early brain development. Mutations in genes involved in early brain wiring and synapse formation and pruning increase the risk for developing autism, further highlighting the relevance of brain development factors in the pathophysiology of neurodevelopmental disorders.
脊椎动物神经系统（包括脑和脊髓）的发育以逐步的方式进行，这涉及数千个基因的功能。新神经元的诞生（也称为神经发生）以及它们随后向发育中脑内适当位置的迁移标志着中枢神经系统发育的最早阶段。随后，这些新生神经元延伸轴突和树突，在发育中的脑内形成定型的突触连接，这是一个复杂的过程，涉及对特定细胞外信号作出反应的细胞内在机制。轴突向脑和身体中其适当靶区域的延伸和导航依赖于许多细胞表面蛋白，这些蛋白检测细胞外线索并将信号转导至细胞内部。反过来，细胞内信号传导机制协调轴突结构重组以及朝着或远离引导线索的适当转向。一旦到达靶区域，轴突与靶细胞之间就会形成化学突触，同样，这似乎涉及细胞表面蛋白向神经元内部发出信号，以使突触稳定并成熟。在这里，我们描述了一些在早期脑发育中调节轴突导向和突触形成的关键趋同且在某些情况下趋异的分子途径。参与早期脑布线以及突触形成和修剪的基因突变会增加患自闭症的风险，这进一步凸显了脑发育因子在神经发育障碍病理生理学中的相关性。
