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Homeobox genes and the specification of neuronal identity
Nature Reviews Neuroscience ( IF 34.7 ) Pub Date : 2021-08-26 , DOI: 10.1038/s41583-021-00497-x
Oliver Hobert 1
Affiliation  

The enormous diversity of cell types that characterizes any animal nervous system is defined by neuron-type-specific gene batteries that endow cells with distinct anatomical and functional properties. To understand how such cellular diversity is genetically specified, one needs to understand the gene regulatory programmes that control the expression of cell-type-specific gene batteries. The small nervous system of the nematode Caenorhabditis elegans has been comprehensively mapped at the cellular and molecular levels, which has enabled extensive, nervous system-wide explorations into whether there are common underlying mechanisms that specify neuronal cell-type diversity. One principle that emerged from these studies is that transcription factors termed ‘terminal selectors’ coordinate the expression of individual members of neuron-type-specific gene batteries, thereby assigning unique identities to individual neuron types. Systematic mutant analyses and recent nervous system-wide expression analyses have revealed that one transcription factor family, the homeobox gene family, is broadly used throughout the entire C. elegans nervous system to specify neuronal identity as terminal selectors. I propose that the preponderance of homeobox genes in neuronal identity control is a reflection of an evolutionary trajectory in which an ancestral neuron type was specified by one or more ancestral homeobox genes, and that this functional linkage then duplicated and diversified to generate distinct cell types in an evolving nervous system.



中文翻译:

同源盒基因和神经元身份的规范

表征任何动物神经系统的细胞类型的巨大多样性是由神经元类型特异性基因组定义的,这些基因组赋予细胞不同的解剖和功能特性。要了解这种细胞多样性是如何遗传指定的,需要了解控制细胞类型特异性基因组表达的基因调控程序。线虫秀丽隐杆线虫的小神经系统已经在细胞和分子水平上进行了全面的绘制,这使得对神经元细胞类型多样性是否存在共同的潜在机制进行了广泛的、神经系统范围的探索。从这些研究中得出的一个原则是,被称为“终端选择器”的转录因子协调神经元类型特异性基因组的个体成员的表达,从而为个体神经元类型分配独特的身份。系统突变分析和最近的神经系统范围内的表达分析表明,一个转录因子家族,同源框基因家族,在整个秀丽隐杆线虫中广泛使用神经系统将神经元身份指定为终端选择器。我提出在神经元身份控制中同源框基因的优势是进化轨迹的反映,其中一个或多个祖先同源框基因指定了一个祖先神经元类型,然后这种功能联系被复制和多样化以产生不同的细胞类型。一个不断进化的神经系统。

更新日期:2021-08-27
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