Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, U.S.A.
Biochem Soc Trans. 2020 Oct 30;48(5):2101-2115. doi: 10.1042/BST20200261.
Microcephaly is a rare, yet devastating, neurodevelopmental condition caused by genetic or environmental insults, such as the Zika virus infection. Microcephaly manifests with a severely reduced head circumference. Among the known heritable microcephaly genes, a significant proportion are annotated with centrosome-related ontologies. Centrosomes are microtubule-organizing centers, and they play fundamental roles in the proliferation of the neuronal progenitors, the neural stem cells (NSCs), which undergo repeated rounds of asymmetric cell division to drive neurogenesis and brain development. Many of the genes, pathways, and developmental paradigms that dictate NSC development in humans are conserved in Drosophila melanogaster. As such, studies of Drosophila NSCs lend invaluable insights into centrosome function within NSCs and help inform the pathophysiology of human microcephaly. This mini-review will briefly survey causative links between deregulated centrosome functions and microcephaly with particular emphasis on insights learned from Drosophila NSCs.
小头畸形是一种罕见但严重的神经发育障碍，由遗传或环境因素引起，如寨卡病毒感染。小头畸形的表现为头围严重减小。在已知的遗传性小头畸形基因中，有相当一部分被注释为与中心体相关的本体论。中心体是微管组织中心，它们在神经元前体细胞（神经干细胞，NSCs）的增殖中发挥着基本作用，NSCs 经历多次不对称细胞分裂以驱动神经发生和大脑发育。许多决定人类 NSCs 发育的基因、途径和发育范例在黑腹果蝇中是保守的。因此，对果蝇 NSCs 的研究为 NSCs 中的中心体功能提供了宝贵的见解，并有助于阐明人类小头畸形的病理生理学。这篇简短的综述将简要调查失调的中心体功能与小头畸形之间的因果关系，特别强调从果蝇 NSCs 中获得的见解。
