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Cells 2023 Sep 28;1219:. doi: 10.3390/cells12192379.
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Purine Biosynthesis Pathways Are Required for Myogenesis in Xenopus laevis.

Duperray M , Hardet F , Henriet E , Saint-Marc C , Boué-Grabot E , Daignan-Fornier B , Massé K , Pinson B .

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.

PubMed ID: 37830593
PMC ID: PMC10571971
Article link: Cells
Grant support: [+]

Species referenced: Xenopus tropicalis Xenopus laevis
Genes referenced: adsl hprt1 lbx1 mespa myf5 myod1 myrf odc1 pam pax3 ppat tbxt tcf15 xpnpep1
GO keywords: purinergic nucleotide receptor signaling pathway [+]
Antibodies: Newt Ab1
Morpholinos: adsl MO1 adsl MO2 hprt1 MO1

Article Images: [+] show captions
References [+] :
Balasubramaniam, Inborn errors of purine metabolism: clinical update and therapies. 2014, Pubmed