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Spermatogenic signaling through Rarg

Shosei Yoshida and colleagues report that differential expression of the retinoic acid (RA) receptor γ gene (Rarg) between two self-renewing subpopulations of undifferentiated spermotogonia controls the response to differentiation signals (Development 142, 1582–1592, 2015). In mouse seminiferous tubules, differentiating and undifferentiated, self-renewing germ cells comingle. This is in contrast to closed stem cell niches, such as the Drosophila testicular hub, in which undifferentiated and differentiating cells are spatially separated. Using a vitamin A–deficient mouse model, Yoshida and colleagues found that the GFRα1+ stem cell population does not depend on RA signaling for self-renewal or differentiation into NGN3+ cells, a poised cell population that normally differentiates further into KIT+ spermotogonia and finally into spermatocytes. However, NGN3+ cells cannot differentiate into KIT+ cells in the absence of vitamin A. The authors found that Rarg was differentially expressed between the NGN3+ and GRFα1+ subpopulations and that Rarg expression was necessary for the response of NGN3+ cells to RA. Finally, they showed that enforced expression of Rarg was sufficient to cause the stem cell population to differentiate directly into KIT+ cells, skipping the NGN3+ stage. These results provide insight into how cell fate decisions can be regulated within open stem cell niches.

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LaFlamme, B. Spermatogenic signaling through Rarg. Nat Genet 47, 568 (2015). https://doi.org/10.1038/ng.3327

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