Haldipur Parthiv, Dang Derek, Millen Kathleen J
Seattle Children's Research Institute, Center for Integrative Brain Research, Seattle, WA, United States.
Seattle Children's Research Institute, Center for Integrative Brain Research, Seattle, WA, United States; Department of Pediatrics, Genetics Division, University of Washington, Seattle, WA, United States.
Handb Clin Neurol. 2018;154:29-44. doi: 10.1016/B978-0-444-63956-1.00002-3.
With the growing recognition of the extent and prevalence of human cerebellar disorders, an understanding of developmental programs that build the mature cerebellum is necessary. In this chapter we present an overview of the basic epochs and key molecular regulators of the developmental programs of cerebellar development. These include early patterning of the cerebellar territory, the genesis of cerebellar cells from multiple spatially distinct germinal zones, and the extensive migration and coordinated cellular rearrangements that result in the formation of the exquisitely foliated and laminated mature cerebellum. This knowledge base is founded on extensive analysis of animal models, particularly mice, due in large part to the ease of genetic manipulation of this important model organism. Since cerebellar structure and function are largely conserved across species, mouse cerebellar development is highly relevant to humans and has led to important insights into the developmental pathogenesis of human cerebellar disorders. Human fetal cerebellar development remains largely undescribed; however, several human-specific developmental features are known which are relevant to human disease and underline the importance of ongoing human fetal research.
随着对人类小脑疾病的范围和患病率的认识不断提高，了解构建成熟小脑的发育程序变得十分必要。在本章中，我们概述了小脑发育程序的基本阶段和关键分子调节因子。这些包括小脑区域的早期模式形成、来自多个空间上不同生发区的小脑细胞的产生，以及广泛的迁移和协调的细胞重排，这些过程导致了精致的叶状和分层的成熟小脑的形成。这一知识库建立在对动物模型，特别是小鼠的广泛分析基础上，这在很大程度上是由于对这种重要模型生物进行基因操作比较容易。由于小脑的结构和功能在物种间基本保守，小鼠小脑发育与人类高度相关，并为深入了解人类小脑疾病的发育发病机制提供了重要见解。人类胎儿小脑发育在很大程度上仍未被描述；然而，已知一些与人类疾病相关的人类特有的发育特征，这突出了正在进行的人类胎儿研究的重要性。
