Striated muscles that enable mouth opening and swallowing during feeding are essential for efficient energy acquisition, and are likely to have played a fundamental role in the success of early jawed vertebrates. The developmental origins and genetic requirements of these muscles are uncertain. Here, we determine by indelible lineage tracing in mouse that fibres of sternohyoid muscle (SHM), which is essential for mouth opening during feeding, and oesophageal striated muscle (OSM), which is crucial for voluntary swallowing, arise from Pax3-expressing somite cells. In vivo Kaede lineage tracing in zebrafish reveals the migratory route of cells from the anteriormost somites to OSM and SHM destinations. Expression of pax3b, a zebrafish duplicate of Pax3, is restricted to the hypaxial region of anterior somites that generate migratory muscle precursors (MMPs), suggesting that Pax3b plays a role in generating OSM and SHM. Indeed, loss of pax3b function led to defective MMP migration and OSM formation, disorganised SHM differentiation, and inefficient ingestion and swallowing of microspheres. Together, our data demonstrate Pax3-expressing somite cells as a source of OSM and SHM fibres, and highlight a conserved role of Pax3 genes in the genesis of these feeding muscles of vertebrates.
Funding
J.E.N.M. was supported by an Medical Research Council (MRC) PhD studentship and an American Heart Association Postdoctoral Fellowship [11POST7360004]. C.-M.F. and S.L. were supported by a National Institutes of Health grant [AR060042] and the Carnegie Endowment. J.F.R. was supported by a Pew Scholars in the Biomedical Sciences Award. S.M.H. is a member of MRC External Scientific Staff with Programme Grant [G1001029] support. Deposited in PMC for release after 6 months.
Author contributions
J.E.N.M. and S.M.H. designed the study. J.E.N.M. performed the fish experiments with help from Y.H., S.M.H. and P.T. V.C.W. performed most mouse experiments. S.L. and C.-M.F. did the tamixofen and Wnt1Cre experiments. S.M.H., C.-M.F. and J.F.R. obtained the funding. J.E.N.M. and S.M.H. wrote the manuscript with input from all authors.