Purine Biosynthesis Pathways Are Required for Myogenesis in 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 mainly 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), which is an enzyme required for both salvage and de novo purine pathways. adsl.L knockdown led to a severe reduction in the expression of the myogenic regulatory factors (MRFs: Myod1, Myf5 and Myogenin), thus resulting in defects in somite formation and, at later stages, the development and/or migration of both craniofacial and hypaxial muscle progenitors. The reduced expressions of hprt1.L and ppat, which are two genes specific to the salvage and de novo pathways, respectively, resulted in similar alterations. In conclusion, our data show for the first time that de novo and recycling purine pathways are essential for myogenesis and highlight new mechanisms in the regulation of MRF gene expression.

Appendage regeneration requires IMPDH2 and creates a sensitized environment for enzyme filament formation

“…Notably, other enzymes in the purine biosynthesis pathway, specifically adenylosuccinate lyase (ADSL), are required for muscle development in Xenopus. 24 Patient alleles of IMPDH2 that affect filament formation are associated with motor deficits, which may be attributable to changes in purinogenesis in either muscle cells, neurons, or both. 3 IMPDH2 function is also required for development of the enteric nervous system in mice.…”