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Retinoic Acid Receptors Control Spermatogonia Cell-Fate and Induce Expression of the SALL4A Transcription Factor


Differentiation of spermatozoa from immature germ cells, called spermatogonia, critically depends on retinoic acid (ATRA), the active metabolite of vitamin A that acts though binding to nuclear receptors called RXR and RAR. To understand the mechanism by which ATRA control germ cell differentiation, we generated mice simultaneously lacking all RXR or all RAR specifically in spermatogonia. From their phenotypic analysis, we demonstrate that meiosis does not require a RAR/RXR-dependent pathway in germ cells and propose that this process is either ATRA-independent or requires an ATRA signal originating from somatic cells. We also show that RXR, in the form of dimers with RAR, can drive spermatogonia differentiation through binding to a regulatory region located in the Sall4 gene. This finding is significant, as the transcription factor encoded by Sall4 is known to regulate the expression of KIT, a key tyrosine kinase receptor which is frequently deregulated in testicular cancer.


Vyšlo v časopise: Retinoic Acid Receptors Control Spermatogonia Cell-Fate and Induce Expression of the SALL4A Transcription Factor. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005501
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005501

Souhrn

Differentiation of spermatozoa from immature germ cells, called spermatogonia, critically depends on retinoic acid (ATRA), the active metabolite of vitamin A that acts though binding to nuclear receptors called RXR and RAR. To understand the mechanism by which ATRA control germ cell differentiation, we generated mice simultaneously lacking all RXR or all RAR specifically in spermatogonia. From their phenotypic analysis, we demonstrate that meiosis does not require a RAR/RXR-dependent pathway in germ cells and propose that this process is either ATRA-independent or requires an ATRA signal originating from somatic cells. We also show that RXR, in the form of dimers with RAR, can drive spermatogonia differentiation through binding to a regulatory region located in the Sall4 gene. This finding is significant, as the transcription factor encoded by Sall4 is known to regulate the expression of KIT, a key tyrosine kinase receptor which is frequently deregulated in testicular cancer.


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