Purine biosynthesis pathways are required for myogenesisin Xenopus laevis

Abstract

Purines 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 amphibian Xenopus laevis as 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 and de novo purine pathways. adsl.L knock-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 of hprt1.L and ppat, two genes specific to the salvage and the de novo pathways, respectively. In conclusion, our data shows for the first time that de novo and recycling purine pathways are essential for myogenesis and highlight new mechanisms in the regulation of MRFs gene expression.