Neurogenesis, neuronal migration, and axon guidance.
Neurogenesis, neuronal migration, and axon guidance.
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DOI：
10.1016/b978-0-444-64150-2.00004-6
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发表时间：
2020-01-01
影响因子：
--
通讯作者：
Srour, Myriam
中科院分区：
文献类型：
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作者：
Accogli, Andrea;Addour-Boudrahem, Nassima;Srour, Myriam
中枢神经系统（CNS）的发育是一个复杂的动态过程，涉及从早期胚胎阶段到出生后生活的遗传，环境，生物化学和物理因素的精确协调序列。在过去的十年中，通过现代遗传学技术和实验方法的应用，在揭示人类中枢神经系统发育的机制方面取得了长足的进步。在这一章中，我们回顾了目前的知识有关的主要发展过程和信号机制（一）神经发生，（二）神经元迁移，（三）轴突的指导。我们讨论了神经干细胞的增殖，迁移，神经元祖细胞的末端易位，轴突导向和寻路的相关机制。对于每一节，我们还提供了一个全面的概述，基本的监管过程，包括转录，转录后，和表观遗传因子，以及无数的信号通路，是关键的决定神经元祖细胞和新形成的迁移神经元的命运。我们进一步强调了这个复杂的调节系统的损伤，如其核心成分的突变，可能会导致人类皮质畸形，癫痫，智力残疾和自闭症。因此，对正常人类CNS发育的透彻理解对于解释神经发育障碍的机制至关重要，并反过来指导有效和有针对性的治疗策略的发展。
Development of the central nervous system (CNS) is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical factors from early embryonic stages to postnatal life. Duringthe past decade, great strides have been made to unravel mechanisms underlying human CNS development through the employment of modern genetic techniques and experimental approaches. In this chapter, we review the current knowledge regarding the main developmental processes and signaling mechanisms of (i) neurogenesis, (ii) neuronal migration, and (iii) axon guidance. We discuss mechanisms related to neural stem cells proliferation, migration, terminal translocation of neuronal progenitors, and axon guidance and pathfinding. For each section, we also provide a comprehensive overview of the underlying regulatory processes, including transcriptional, posttranscriptional, and epigenetic factors, and a myriad of signaling pathways that are pivotal to determine the fate of neuronal progenitors and newly formed migrating neurons. We further highlight how impairment of this complex regulating system, such as mutations in its core components, may cause cortical malformation, epilepsy, intellectual disability, and autism in humans. A thorough understanding of normal human CNS development is thus crucial to decipher mechanisms responsible for neurodevelopmental disorders and in turn guide the development of effective and targeted therapeutic strategies.