ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2020) 17 6.5 | DOI: 10.1530/ey.17.6.5


To read the full abstract: FASEB J. 2019, Jul; 33: 8423–35. doi: https://www.ncbi.nlm.nih.gov/pubmed/30991836

Retinoic acid (RA) is essential for the regulation of many developmental events including germ cell differentiation. In the developing testis, tight spatiotemporal control of RA levels is maintained by the enzyme CYP26B1, which inactivates RA. CYP26B1 expression is regulated by SOX9 and NR5A1/SF1 in Sertoli cells, but the mechanism that modulates its activity postnatally to allow germ cell differentiation from the niche of spermatogonial sperm cells was unknown. Here, Parekh et al performed in vivo and in vitro studies using mouse and cell models to reveal the underlying regulation. They found that NOTCH signaling through HEY1 and other transcription factor represses CYP26B1 activity. They also show that Sertoli cells receiving NOTCH signaling by ligand JAG1 trigger germ cell differentiation by down-regulation of CYP26B1.

Studies investigating developmental regulation of germ cell differentiation enhance our understanding of basic biology. They reveal essential information to develop protocols for stem cell-based treatment opportunities for DSDs and for infertility in general.

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