Feng Xuesong, Adiarte Eric G, Devoto Stephen H
Department of Biology, Wesleyan University, Middletown, CT 06459, USA.
Dev Biol. 2006 Dec 15;300(2):736-46. doi: 10.1016/j.ydbio.2006.08.056. Epub 2006 Aug 30.
Vertebrate myogenesis is regulated by signaling proteins secreted from surrounding tissues. One of the most important, Sonic hedgehog, has been proposed to regulate myogenic precursor cell survival, proliferation, and differentiation in a variety of vertebrates. In zebrafish, Hedgehog signaling is both necessary and sufficient for the development of embryonic slow muscle fibers-the earliest differentiating muscle fibers. Here we investigated the function of Hedgehog signaling in another zebrafish myogenic lineage, a dermomyotomal population of cells defined by somitic pax3/7 expression. We found that Hedgehog negatively regulates the number of myogenic precursors expressing pax3/7. Hh also positively regulates the growth of embryonic fast muscle. Unlike Hedgehog's function in regulating the elongation of fast muscle fibers, this regulation is not mediated by embryonic slow muscle fibers. Instead, it is a direct Hedgehog response, cell autonomous to myogenic precursors. The regulation of myogenic precursors and their differentiation into fast fibers have a different critical time period for Hh signaling, and different requirements for specific gli gene family members of Hh activated transcription factors from the earlier promotion of embryonic slow muscle fiber differentiation. We propose that Hedgehog signaling acts at multiple times on different lineages, through different downstream pathways, to promote myogenic differentiation.
脊椎动物的肌生成受周围组织分泌的信号蛋白调控。其中最重要的一种信号蛋白，即音猬因子，被认为在多种脊椎动物中调节成肌前体细胞的存活、增殖和分化。在斑马鱼中，刺猬信号通路对于胚胎慢肌纤维（最早分化的肌纤维）的发育既是必需的也是充分的。在此，我们研究了刺猬信号通路在斑马鱼另一个成肌谱系中的功能，这个谱系是由体节中pax3/7表达所定义的生皮肌节细胞群体。我们发现刺猬信号通路负向调节表达pax3/7的成肌前体细胞数量。音猬因子还正向调节胚胎快肌的生长。与刺猬信号通路在调节快肌纤维伸长方面的功能不同，这种调节不是由胚胎慢肌纤维介导的。相反，这是一种直接的刺猬信号反应，对成肌前体细胞具有细胞自主性。成肌前体细胞的调节及其向快肌纤维的分化对于刺猬信号通路有不同的关键时期，并且与早期促进胚胎慢肌纤维分化相比，对刺猬信号激活转录因子的特定gli基因家族成员有不同的需求。我们提出，刺猬信号通路通过不同的下游途径在多个时间点作用于不同谱系，以促进成肌分化。
