UPMC Paris 06, UMR-S 787, F-75013 Paris, France.
Dev Cell. 2011 Aug 16;21(2):273-87. doi: 10.1016/j.devcel.2011.06.019. Epub 2011 Jul 21.
Coordinating the balance between progenitor self-renewal and myogenic differentiation is required for a regulated expansion of the developing muscles. Previous observation that neural crest cells (NCCs) migrate throughout the somite regions, where trunk skeletal muscles first emerge, suggests a potential role for these cells in influencing early muscle formation. However, specific signaling interactions between NCCs and skeletal muscle cells remain unknown. Here we show that mice with specific NCC and peripheral nervous system defects display impaired survival of skeletal muscle and show skeletal muscle progenitor cell (MPC) depletion due to precocious commitment to differentiation. We show that reduced NCC-derived Neuregulin1 (Nrg1) in the somite region perturbs ErbB3 signaling in uncommitted MPCs. Using a combination of explant culture experiments and genetic ablation in the mouse, we demonstrate that Nrg1 signals provided by the NCC lineage play a critical role in sustainable myogenesis, by restraining MPCs from precocious differentiation.
协调祖细胞自我更新和肌生成分化之间的平衡对于发育中的肌肉的调节性扩张是必需的。先前的观察表明，神经嵴细胞（NCC）迁移到躯干部位的体节区域，这些区域是最初出现躯干骨骼肌肉的地方，这表明这些细胞在影响早期肌肉形成方面可能发挥作用。然而，NCC 和骨骼肌肉细胞之间的特定信号相互作用仍然未知。在这里，我们发现具有特定 NCC 和周围神经系统缺陷的小鼠显示出骨骼肌肉存活受损，并显示出骨骼肌肉祖细胞（MPC）耗竭，这是由于过早分化。我们发现，体节区域中 NCC 衍生的神经调节蛋白 1（Nrg1）的减少会扰乱未分化 MPC 中的 ErbB3 信号。通过组合使用外植体培养实验和在小鼠中的基因缺失，我们证明 NCC 谱系提供的 Nrg1 信号通过抑制 MPC 过早分化，在可持续的成肌作用中发挥关键作用。
