ABSTRACT
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.
Footnotes
Author contributions
Conceptualization: C.A.F., E.R.G.; Methodology: C.S., L.M.W., A.P., M.S.-P., C.A.F., E.R.G.; Formal analysis: C.S., L.M.W.; Investigation: C.S., L.M.W., A.P.; Resources: A.P., C.A.F.; Writing - original draft: C.S., L.M.W., E.R.G.; Writing - review & editing: C.S., L.M.W., A.P., C.A.F., E.R.G.; Supervision: E.R.G.; Project administration: E.R.G.; Funding acquisition: C.A.F., E.R.G.
Funding
This work was supported by the European Research Council (H2020GA 810207-ARPCOMPLEXITY and FP7-GA 617676 PHONICS to E.R.G.); a European Molecular Biology Organization Installation Grant (2758 to E.R.G.); AFM-Téléthon (21661); Congento (LISBOA-01-0145-FEDER-022170), co-financed by Fundação para a Ciência e a Tecnologia and Lisboa2020, under the PORTUGAL2020 agreement (European Regional Development Fund); Fundação para a Ciência e Tecnologia (2022.09228.|PTDC; PTDC/MED-ANM/7695/2020; 2021.04013.CEECIND to C.A.F.); Foundation Leducq (ATTRACT, 17CVD03 to C.A.F.); and ‘la Caixa’ Foundation (ECARD, LCF/PR/HR22/52420027 to C.A.F.). C.S. (2020.04642.BD) and A.P. (SFRH/BD/130635/2017 and COVID/BD/152399/2022) were supported by fellowships from the Fundação para a Ciência e a Tecnologia.
Data availability
All relevant data can be found within the article and its supplementary information.
