The B-cell maturation factor Blimp-1 specifies vertebrate slow-twitch muscle fiber identity in response to Hedgehog signaling
The B-cell maturation factor Blimp-1 specifies vertebrate slow-twitch muscle fiber identity in response to Hedgehog signaling
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DOI：
10.1038/ng1280
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发表时间：
2004-01-01
期刊：
影响因子：
30.8
通讯作者：
Roy, S
中科院分区：
文献类型：
--
作者：
Baxendale, S;Davison, C;Roy, S
脊椎动物骨骼肌由不同的纤维类型组成，它们的形态、收缩功能、线粒体含量和代谢特性都不同。最近的研究发现，转录辅助激活因子PGC-1是调节胚胎后发育中纤维型可塑性的生理刺激的关键介质(1)。尽管成肌细胞在发育早期注定要分化成不同种类的纤维，但决定胚胎纤维类型规格的调节蛋白的身份仍然不清楚。在这里，我们证明了基因u-Boot(Ubo)，一种破坏胚胎慢抽动纤维诱导的突变(2)，编码了Blimp-1的斑马鱼同源物，Blimp-1是一个包含转录因子的设定区域，促进哺乳动物B淋巴细胞的终末分化(3)。Ubo的表达是由Hedgehog(HH)信号在预期的慢肌前体中诱导的，其活性本身就足以指导幼稚成肌细胞对慢抽动纤维的特定发育。我们的数据首次提供了对脊椎动物胚胎中特定的一组肌肉前体被驱动沿着不同的纤维类型分化路径响应位置线索的机制的分子洞察。
Vertebrate skeletal muscles comprise distinct fiber types that differ in their morphology, contractile function, mitochondrial content and metabolic properties. Recent studies identified the transcriptional coactivator PGC-1 as a key mediator of the physiological stimuli that modulate fiber-type plasticity in postembryonic development(1). Although myoblasts become fated to differentiate into distinct kinds of fibers early in development, the identities of regulatory proteins that determine embryonic fiber-type specification are still obscure. Here we show that the gene u-boot (ubo), a mutation in which disrupts the induction of embryonic slow-twitch fibers(2), encodes the zebrafish homolog of Blimp-1, a SET domain containing transcription factor that promotes the terminal differentiation of B lymphocytes in mammals(3). Expression of ubo is induced by Hedgehog (Hh) signaling in prospective slow muscle precursors, and its activity alone is sufficient to direct slow-twitch fiber specific development by naive myoblasts. Our data provide the first molecular insight into the mechanism by which a specific group of muscle precursors is driven along a distinct pathway of fiber-type differentiation in response to positional cues in the vertebrate embryo.