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Hedgehog 信号通路和层粘连蛋白在肌肉发育中发挥独特的协同作用。

Hedgehog signaling and laminin play unique and synergistic roles in muscle development.

机构信息

School of Biology and Ecology, University of Maine, Orono, Maine 04469, USA.

出版信息

Dev Dyn. 2010 Mar;239(3):905-13. doi: 10.1002/dvdy.22204.

Abstract

Hedgehog (Hh) signaling and laminin-111, a basement membrane protein, are required for early muscle development. Hh signaling specifies different populations of muscle fibers and laminin-111 is critical for early muscle morphogenesis. However, additional requirements for Hh signaling and laminin during later phases of muscle development are not known. Furthermore, interactions between Hh signaling and laminin in this context are unknown. We used laminin gamma1 mutant zebrafish and cyclopamine to block Hh signal transduction separately and in combination to investigate their functions and interactions. We found that both Hh signaling and laminin are required for normal myosin chain expression. In addition, Hh signaling and laminin act synergistically during fast-twitch fiber elongation: fast muscle cells do not elongate in embryos deficient for both Hh signaling and laminin. Finally, we present evidence that suggests that Hh signaling is indirectly required via slow fiber specification for recovery of fast fiber elongation in laminin gamma1 mutant embryos.

摘要

Hedgehog (Hh) 信号通路和层粘连蛋白-111(一种基底膜蛋白)对于早期肌肉发育是必需的。Hh 信号通路指定了不同的肌肉纤维群体,而层粘连蛋白-111 对于早期肌肉形态发生至关重要。然而,在肌肉发育的后期阶段,Hh 信号通路和层粘连蛋白仍有其他需求尚不清楚。此外,在这种情况下,Hh 信号通路和层粘连蛋白之间的相互作用也未知。我们分别使用层粘连蛋白γ1 突变斑马鱼和环巴胺来阻断 Hh 信号转导,并将其组合使用,以研究它们的功能和相互作用。我们发现,Hh 信号通路和层粘连蛋白对于正常肌球蛋白链表达都是必需的。此外,在快速肌纤维伸长过程中,Hh 信号通路和层粘连蛋白协同作用:缺乏 Hh 信号通路和层粘连蛋白的胚胎中,快速肌细胞不会伸长。最后,我们提供的证据表明,通过慢肌纤维的特化,Hh 信号通路间接地对层粘连蛋白γ1 突变胚胎中快速肌纤维伸长的恢复是必需的。

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