Haldipur Parthiv, 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; University of Washington, Department of Pediatrics, Division of Genetics, Seattle, WA, United States.
Neurosci Lett. 2019 Jan 1;688:14-25. doi: 10.1016/j.neulet.2018.05.032. Epub 2018 May 23.
Structural birth defects of the cerebellum, or cerebellar malformations, in humans, have long been recognized. However, until recently there has been little progress in elucidating their developmental pathogenesis. Innovations in brain imaging and human genetic technologies over the last 2 decades have led to better classifications of these disorders and identification of several causative genes. In contrast, cerebellar malformations in model organisms, particularly mice, have been the focus of intense study for more than 70 years. As a result, many of the molecular, genetic and cellular programs that drive formation of the cerebellum have been delineated in mice. In this review, we overview the basic epochs and key molecular regulators of the developmental programs that build the structure of the mouse cerebellum. This mouse-centric approach has been a useful to interpret the developmental pathogenesis of human cerebellar malformations. However, it is becoming apparent that we actually know very little regarding the specifics of human cerebellar development beyond what is inferred from mice. A better understanding of human cerebellar development will not only facilitate improved diagnosis of human cerebellar malformations, but also lead to the development of treatment paradigms for these important neurodevelopmental disorders.
人类小脑的结构性出生缺陷，即小脑畸形，早已为人所知。然而，直到最近，在阐明其发育发病机制方面进展甚微。过去20年里脑成像和人类基因技术的创新，使得对这些疾病有了更好的分类，并鉴定出了多个致病基因。相比之下，模式生物尤其是小鼠中的小脑畸形，70多年来一直是深入研究的焦点。因此，在小鼠中已经阐明了许多驱动小脑形成的分子、遗传和细胞程序。在本综述中，我们概述了构建小鼠小脑结构的发育程序的基本阶段和关键分子调节因子。这种以小鼠为中心的方法有助于解释人类小脑畸形的发育发病机制。然而，很明显，除了从小鼠推断出的内容外，我们实际上对人类小脑发育的具体细节知之甚少。更好地了解人类小脑发育不仅将有助于改善对人类小脑畸形的诊断，还将推动针对这些重要神经发育障碍的治疗模式的发展。
