SEMINAR: Muscle satellite cell dynamics; How does your myofibre grow?

The Seminar: Postnatal growth in mouse is rapid, with total skeletal muscle mass increasing several-fold between birth and weaning (just a few weeks). Where myofibre hypertrophy during growth requires the addition of new myonuclei, these are supplied by muscle satellite cells, the resident stem cells of skeletal muscle. The satellite cell population of adult muscle is largely maintained in number throughout pre-senile life; however severe diminution of the satellite cell compartment does occur during early postnatal growth. We have sought to address the lack of empirical definition in the dynamics of the satellite cell compartment with a detailed assessment of growth dynamics of mouse extensor digitorum longus (EDL) muscles during the first six weeks after birth. We have utilised two mouse models that positively (Myf5nLacZ) or negatively (3FnLacZE) identify satellite cells on isolated myofibres, and compared this to accretion of EDL fibre myonuclei. We find that most myonuclear accretion of EDL fibres occurs within the initial three weeks after birth, and that the absolute and relative size of the satellite cell compartment of individual myofibres drastically decreases over the same period. Neither myonuclear number nor satellite cell proportion significantly alter after three weeks of age up to ten months of age, indicating that the adult configuration of satellite cell-myofibre dynamics is established very early on in post-natal life. Some very elegant studies have demonstrated that the transcription factor Pax7 is required for satellite cell function during this postnatal growth period, but that its function later becomes dispensable. We have investigated the role of Pax7 in controlling the transcriptional landscape of satellite cells using cell biology, microarrays, ChIP and next-generation sequencing to provide an in-depth analysis of transcription factor function in a model stem cell. This approach has uncovered interesting new players in satellite cell biology, and revealed some new tricks for an old dog.

The Speaker: Rob was awarded his PhD in developmental biology from ECU, and completed a postdoc at the Randall division of King's College London. Working in Pete Zammit's lab, he investigated transcriptional signalling in satellite cell progression, the contribution of satellite cells to postnatal growth, and the role of satellite cells in several dystrophic knockout mice. He is now back in WA, taking up a postdoc at the Parkinson's Centre, ECU.