Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal.
Universidade Católica Portuguesa, Católica Medical School, Católica Biomedical Research Centre, 1649-023, Lisbon, Portugal.
Development. 2024 Oct 1;151(19). doi: 10.1242/dev.202548. Epub 2024 Oct 4.
Skeletal muscle development is a complex process involving myoblast fusion to generate multinucleated fibers. Myonuclei first align in the center of the myotubes before migrating to the periphery of the myofiber. Blood vessels (BVs) are important contributors to the correct development of skeletal muscle, and myonuclei are found next to BVs in adult muscle. Here, we show that most myonuclear migration to the periphery occurs between embryonic day 17.5 and postnatal day 1 in mouse. Furthermore, myonuclear accretion after postnatal day 7 does not result in centrally nucleated myofibers as observed in the embryo. Instead, myonuclei remain at the periphery of the myofiber without moving to the center. Finally, we show that hypovascularization of skeletal muscle alters the interaction between myonuclei and BVs, suggesting that BVs may contribute to myonuclear positioning during skeletal muscle postnatal development. Overall, this work provides a comprehensive analysis of skeletal muscle development during the highly dynamic postnatal period, bringing new insights about myonuclear positioning and its interaction with BVs.
骨骼肌的发育是一个复杂的过程，涉及成肌细胞融合以产生多核纤维。肌细胞核首先在肌管的中心排列，然后迁移到肌纤维的外围。血管（BVs）是骨骼肌正常发育的重要贡献者，在成年肌肉中，肌细胞核位于 BVs 旁边。在这里，我们发现在小鼠中，大多数肌核向周边的迁移发生在胚胎第 17.5 天到出生后第 1 天之间。此外，出生后第 7 天以后的肌核积累不会导致胚胎中观察到的中央核化肌纤维。相反，肌细胞核仍然位于肌纤维的外围，不会移动到中心。最后，我们发现骨骼肌的血管生成不足会改变肌细胞核和 BVs 之间的相互作用，这表明 BVs 可能有助于骨骼肌出生后发育过程中的肌核定位。总的来说，这项工作对出生后高度动态的骨骼肌发育进行了全面分析，为肌核定位及其与 BVs 的相互作用提供了新的见解。
