Esteves de Lima Joana, Bonnin Marie-Ange, Birchmeier Carmen, Duprez Delphine
CNRS UMR 7622, F-75005 Paris, France.
Sorbonne Universités, UPMC Univ Paris 06, Paris, France.
Elife. 2016 Aug 24;5:e15593. doi: 10.7554/eLife.15593.
The importance of mechanical activity in the regulation of muscle progenitors during chick development has not been investigated. We show that immobilization decreases NOTCH activity and mimics a NOTCH loss-of-function phenotype, a reduction in the number of muscle progenitors and increased differentiation. Ligand-induced NOTCH activation prevents the reduction of muscle progenitors and the increase of differentiation upon immobilization. Inhibition of NOTCH ligand activity in muscle fibers suffices to reduce the progenitor pool. Furthermore, immobilization reduces the activity of the transcriptional co-activator YAP and the expression of the NOTCH ligand JAG2 in muscle fibers. YAP forced-activity in muscle fibers prevents the decrease of JAG2 expression and the number of PAX7+ cells in immobilization conditions. Our results identify a novel mechanism acting downstream of muscle contraction, where YAP activates JAG2 expression in muscle fibers, which in turn regulates the pool of fetal muscle progenitors via NOTCH in a non-cell-autonomous manner.
在鸡胚胎发育过程中，机械活动对肌肉祖细胞调控的重要性尚未得到研究。我们发现，固定化会降低NOTCH活性，并模拟NOTCH功能丧失的表型，即肌肉祖细胞数量减少且分化增加。配体诱导的NOTCH激活可防止固定化后肌肉祖细胞数量的减少和分化的增加。抑制肌肉纤维中的NOTCH配体活性足以减少祖细胞池。此外，固定化会降低转录共激活因子YAP的活性以及肌肉纤维中NOTCH配体JAG2的表达。在固定化条件下，肌肉纤维中YAP的强制激活可防止JAG2表达的降低和PAX7+细胞数量的减少。我们的研究结果确定了一种在肌肉收缩下游起作用的新机制，其中YAP激活肌肉纤维中的JAG2表达，进而通过NOTCH以非细胞自主方式调节胎儿肌肉祖细胞池。
