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进化的线索能否揭示小脑的分子发育?

Can clues from evolution unlock the molecular development of the cerebellum?

机构信息

MRC Centre for Developmental Neurobiology, King's College London, 4th floor New Hunt's House, Guy's Campus, London SE1 1UL, UK.

出版信息

Mol Neurobiol. 2011 Feb;43(1):67-76. doi: 10.1007/s12035-010-8160-2. Epub 2010 Dec 21.

DOI:10.1007/s12035-010-8160-2
PMID:21174175
Abstract

The cerebellum sits at the rostral end of the vertebrate hindbrain and is responsible for sensory and motor integration. Owing to its relatively simple architecture, it is one of the most powerful model systems for studying brain evolution and development. Over the last decade, the combination of molecular fate mapping techniques in the mouse and experimental studies, both in vitro and in vivo, in mouse and chick have significantly advanced our understanding of cerebellar neurogenesis in space and time. In amniotes, the most numerous cell type in the cerebellum, and indeed the brain, is the cerebellar granule neurons, and these are born from a transient secondary proliferative zone, the external granule layer (EGL), where proliferation is driven by sonic hedgehog signalling and causes cerebellar foliation. Recent studies in zebrafish and sharks have shown that while the molecular mechanisms of neurogenesis appear conserved across vertebrates, the EGL as a site of shh-driven transit amplification is not, and is therefore implicated as a key amniote innovation that facilitated the evolution of the elaborate foliated cerebella found in birds and mammals. Ellucidating the molecular mechanisms underlying the origin of the EGL in evolution could have significant impacts on our understanding of the molecular details of cerebellar development.

摘要

小脑位于脊椎动物后脑的前端,负责感觉和运动的整合。由于其相对简单的结构,它是研究大脑进化和发育的最强大的模型系统之一。在过去的十年中,在小鼠中的分子命运映射技术的组合,以及在小鼠和鸡中的体外和体内的实验研究,大大提高了我们对小脑神经发生在空间和时间上的理解。在羊膜动物中,小脑甚至大脑中数量最多的细胞类型是小脑颗粒神经元,它们起源于短暂的次级增殖区,即外颗粒层(EGL),那里的增殖是由 sonic hedgehog 信号驱动的,导致小脑叶片形成。最近在斑马鱼和鲨鱼中的研究表明,尽管神经发生的分子机制在脊椎动物中似乎是保守的,但作为 shh 驱动的过渡扩增的 EGL 却不是,因此它被认为是一种关键的羊膜动物创新,促进了在鸟类和哺乳动物中发现的精细叶片状小脑的进化。阐明 EGL 在进化中的起源的分子机制可能对我们理解小脑发育的分子细节有重大影响。

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