Genetic evidence for pax-3 function in myogenesis in the nematode Pristionchus pacificus

PAX3 is a member of the PAX3/7 subfamily of the paired box proteins. In vertebrates, Pax3 is essential for skeletal myogenesis by activating a cascade of transcriptional events that are necessary and sufficient for skeletal myogenesis. Four related basic helix-loop-helix transcription factors, MyoD, Myf5, Mrf4, and Myogenin, are targets of PAX3 and serve as myogenic regulatory factors. Although the role of Pax3 in myogenesis is well studied in vertebrates, little is known about invertebrate PAX-3 proteins and myogenesis. Here, we took advantage of viable alleles of pax-3 in the nematode satellite model organism Pristionchus pacificus to investigate the function of PAX-3 in myogenesis. Two strong reduction-of-function alleles of Ppa-pax-3 show severe muscle-derived abnormalities and phalloidin staining indicates a disruption of body wall muscle patterning. Furthermore, we identified a myogenic regulatory factor-related gene Ppa-hlh-1/MyoD and a serum response factor-related gene Ppa-unc-120. Expression of both genes in Ppa-pax-3 mutant animals is down regulated suggesting that Ppa-pax-3 acts upstream in the regulatory network. Together, our results provide the first genetic evidence for a conserved function of PAX-3 in myogenesis between vertebrates and nematodes.