Modular long-range regulation of Myf5 reveals unexpected heterogeneity between skeletal muscles in the mouse embryo.
Modular long-range regulation of Myf5 reveals unexpected heterogeneity between skeletal muscles in the mouse embryo.
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发表时间：
2000-10
期刊：
影响因子：
4.6
通讯作者：
J. Hadchouel;S. Tajbakhsh;M. Primig;T. Chang;P. Daubas;D. Rocancourt;M. Buckingham
中科院分区：
文献类型：
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作者：
J. Hadchouel;S. Tajbakhsh;M. Primig;T. Chang;P. Daubas;D. Rocancourt;M. Buckingham
肌生成因子Myf 5在肌细胞决定中起关键作用，响应导致肌肉祖细胞特化的信号级联。我们已经通过了YAC转基因的方法，以确定调控序列，指导复杂的时空表达的基因在小鼠胚胎中的肌肉发生。具有不同性质的重要调控区分布在Myf 5基因上游96 kb以上。近端23 kb区域指导鳃弓、轴上皮肌节和肌节中央部分、轴上插入结构域中的早期表达。在胚胎中骨骼肌形成的大多数位点的稳健表达取决于位于Myf 5基因-58至-48 kb之间的增强子样序列。该元件在轴上和轴下肌节、肢体肌肉、舌下神经索中以及在大脑的前体p1和p4中的Myf 5转录位点中是活跃的。然而，Myf 5的后期表达依赖于-96和-63 kb之间的更远端区域，其不作为增强子。这种成分对于头部肌肉的表达是必要的，但令人惊讶的是，它只在躯干肌肉的一个子集中起作用，特别是轴下衍生的腹侧体肌肉以及横膈膜和舌头的肌肉。肢体肌肉块中的转基因表达不受去除-96/-63区域的影响。轴上衍生的肌肉和一些轴下肌肉，如肋间肌和肢带肌，也不受影响。因此，该区域揭示了肌肉质量之间意想不到的异质性，这可能与这些部位肌肉发生的不同方面有关。这种调节的异质性可能是所观察到的肌病局限于特定肌肉亚群的基础。
The myogenic factor Myf5 plays a key role in muscle cell determination, in response to signalling cascades that lead to the specification of muscle progenitor cells. We have adopted a YAC transgenic approach to identify regulatory sequences that direct the complex spatiotemporal expression of this gene during myogenesis in the mouse embryo. Important regulatory regions with distinct properties are distributed over 96 kb upstream of the Myf5 gene. The proximal 23 kb region directs early expression in the branchial arches, epaxial dermomyotome and in a central part of the myotome, the epaxial intercalated domain. Robust expression at most sites in the embryo where skeletal muscle forms depends on an enhancer-like sequence located between -58 and -48 kb from the Myf5 gene. This element is active in the epaxial and hypaxial myotome, in limb muscles, in the hypoglossal chord and also at the sites of Myf5 transcription in prosomeres p1 and p4 of the brain. However later expression of Myf5 depends on a more distal region between -96 and -63 kb, which does not behave as an enhancer. This element is necessary for expression in head muscles but strikingly only plays a role in a subset of trunk muscles, notably the hypaxially derived ventral body muscles and also those of the diaphragm and tongue. Transgene expression in limb muscle masses is not affected by removal of the -96/-63 region. Epaxially derived muscles and some hypaxial muscles, such as the intercostals and those of the limb girdles, are also unaffected. This region therefore reveals unexpected heterogeneity between muscle masses, which may be related to different facets of myogenesis at these sites. Such regulatory heterogeneity may underlie the observed restriction of myopathies to particular muscle subgroups.