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骨骼肌肉形成所依赖的基因调控网络和细胞谱系。

Gene regulatory networks and cell lineages that underlie the formation of skeletal muscle.

机构信息

Department of Developmental and Stem Cell Biology, CNRS UMR 3738, Institut Pasteur, 75015 Paris, France

出版信息

Proc Natl Acad Sci U S A. 2017 Jun 6;114(23):5830-5837. doi: 10.1073/pnas.1610605114.

DOI:10.1073/pnas.1610605114
PMID:28584083
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5468682/
Abstract

Skeletal muscle in vertebrates is formed by two major routes, as illustrated by the mouse embryo. Somites give rise to myogenic progenitors that form all of the muscles of the trunk and limbs. The behavior of these cells and their entry into the myogenic program is controlled by gene regulatory networks, where paired box gene 3 () plays a predominant role. Head and some neck muscles do not derive from somites, but mainly form from mesoderm in the pharyngeal region. Entry into the myogenic program also depends on the myogenic determination factor () family of genes, but is not expressed in these myogenic progenitors, where different gene regulatory networks function, with T-box factor 1 () and paired-like homeodomain factor 2 () as key upstream genes. The regulatory genes that underlie the formation of these muscles are also important players in cardiogenesis, expressed in the second heart field, which is a major source of myocardium and of the pharyngeal arch mesoderm that gives rise to skeletal muscles. The demonstration that both types of striated muscle derive from common progenitors comes from clonal analyses that have established a lineage tree for parts of the myocardium and different head and neck muscles. Evolutionary conservation of the two routes to skeletal muscle in vertebrates extends to chordates, to trunk muscles in the cephlochordate and to muscles derived from cardiopharyngeal mesoderm in the urochordate , where a related gene regulatory network determines cardiac or skeletal muscle cell fates. In conclusion, Eric Davidson's visionary contribution to our understanding of gene regulatory networks and their evolution is acknowledged.

摘要

脊椎动物的骨骼肌是通过两种主要途径形成的,如图所示的小鼠胚胎。体节产生成肌祖细胞,形成躯干和四肢的所有肌肉。这些细胞的行为及其进入成肌程序受基因调控网络控制,其中配对盒基因 3 () 发挥主要作用。头部和一些颈部肌肉不是来自体节,而是主要来自咽区的中胚层。进入成肌程序还取决于成肌决定因子 () 基因家族,但在这些成肌祖细胞中不表达,其中不同的基因调控网络起作用,T 盒因子 1 () 和同源盒基因 2 () 作为关键的上游基因。这些肌肉形成的调节基因也是心脏发生的重要参与者,在第二心脏场表达,第二心脏场是心肌的主要来源,也是产生骨骼肌的咽弓中胚层的主要来源。两种类型的横纹肌都来自共同祖先是通过克隆分析得出的,该分析为部分心肌和不同的头颈部肌肉建立了谱系树。脊椎动物中这两种形成骨骼肌的途径的进化保守性延伸到脊索动物,延伸到头索动物的躯干肌肉和尾索动物的心肌和咽心中胚层衍生的肌肉,其中相关的基因调控网络决定心脏或骨骼肌细胞的命运。总之,Eric Davidson 对我们理解基因调控网络及其进化的有远见的贡献得到了认可。

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