Purine biosynthesis pathways are required for myogenesis inXenopus laevis

Abstract

AbstractPurines are required for fundamental biological processes and alterations in their metabolism lead to severe genetic diseases associated with developmental defects whose etiology remains unclear. Here, we studied the developmental requirements for purine metabolism using the amphibianXenopus laevisas a vertebrate model. We provide the first functional characterization of purine pathway-genes and show that these genes are mostly expressed in nervous and muscular embryonic tissues. Morphants were generated to decipher the functions of these genes, with a focus on the adenylosuccinate lyase (ADSL), an enzyme required for both salvage andde novopurine pathways.adsl.Lknock-down leads to severe reduction in the expression of the Myogenic Regulatory Factors (MRFs: Myod1, Myf5 and Myogenin), thus resulting in defects in somitogenesis and in the formation and/or migration of both craniofacial and hypaxial muscle progenitors. Similar alterations were observed upon reduced expression ofhprt1.Landppat, two genes specific to the salvage and thede novopathways, respectively. In conclusion, our data shows for the first time thatde novoand recycling purine pathways are essential for myogenesis and highlight new mechanisms in the regulation of MRFs gene expression.