Pax7a-expressing muscle precursor cells preferentially generate new fibres during larval muscle growth

Abstract Background Pax7 marks and regulates skeletal muscle stem cells across vertebrates. Zebrafish have two Pax7 genes, pax7a and pax7b , both of which are expressed in embryonic and larval muscle precursor cells (mpcs). Here we use transgenic reporters for each gene to reveal their differential expression and regulation in specific regions of the developing myotome. Methods Protein, mRNA and genetic reporters for pax7a and pax7b gene expression, along with genetic manipulations, were used to characterise the origin, character and fate of mpcs in the zebrafish larva. Results Pax7b is expressed before pax7a and mpcs marked strongly by the pax7b reporter contribute to early fast muscle formation but subsequently locate in the central dermomyotome near the horizontal myoseptum, fail to increase in number, and contribute little to larval myogenesis. These pax7b-only cells are largely depleted when factors regulating the central dermomyotome are removed. In contrast, mpcs expressing the pax7a reporter form few embryonic fibres, increase through rapid proliferation, and contribute to both hyperplastic new fibre formation and hypernucleation of existing fibres. Mpcs expressing only the pax7a reporter are concentrated at the epaxial and hypaxial dorsoventral somitic extremes and there contribute to nascent fibre formation through fusion with one another that depends on expression of the fusogenic transcription factor Myogenin. In contrast, mpcs expressing both pax7 reporters, which are less abundant in the dorsoventral somitic extremes, contribute to larval myogenesis primarily by fusion to pre-existing fibres. Regional signals during early somite patterning regulate the relative abundance and location of the three mpc populations, which have not been observed to interconvert (i.e. change marker expression). Conclusion The data suggest that muscle stem cell diversity arises early in primary myogenesis and underpins aspects of muscle growth.