Rhox10, a member of the X-linked mouse reproductive homeobox (Rhox) gene cluster, is a homeobox protein functioning as a transcription factor [4,5]. It is essential for male fertility as it drives the establishment of spermatogonial stem cells (SSCs) [1,3]. Rhox10 acts through a transcription factor signaling cascade, promoting the differentiation of SSC precursors, pro-spermatogonia (ProSG) [1,3]. It also plays a role in regulating the migration of pro-spermatogonia into the SSC niche [3]. Mouse models are valuable for studying Rhox10 due to its conserved functions in mammals [7].

Conditional loss of the entire 33-gene X-linked homeobox gene cluster including Rhox10, or loss of only Rhox10, leads to progressive spermatogenic decline, resulting from dramatically reduced SSC generation [3]. This indicates Rhox10's crucial role in SSC establishment. In vitro ProSG differentiation assay shows that Rhox10 promotes mouse ProSG differentiation through a conserved transcriptional cascade involving key germ-cell transcription factors DMRT1 and ZBTB16 [1]. Rhox10 also suppresses LINE1 transposition during fetal development in vivo by inducing Piwil2, a key component in the Piwi-interacting RNA pathway protecting against transposable elements [6].

In conclusion, Rhox10 is vital for SSC establishment, ProSG differentiation, and transposon defense in male germ cells. The study of Rhox10 using gene knockout (KO) and conditional knockout (CKO) mouse models has provided insights into germ cell development and may have implications for understanding male infertility [1,3,6].

References:

1. Tan, Kun, Song, Hye-Won, Wilkinson, Miles F. . RHOX10 drives mouse spermatogonial stem cell establishment through a transcription factor signaling cascade. In Cell reports, 36, 109423. doi:10.1016/j.celrep.2021.109423. https://pubmed.ncbi.nlm.nih.gov/34289349/

2. Gerhardt, Katie. 2016. RHOX10 Spurs on Spermatogonial Stem Cell Establishment. In Biology of reproduction, 95, 118. doi:. https://pubmed.ncbi.nlm.nih.gov/27908878/

3. Song, Hye-Won, Bettegowda, Anilkumar, Lake, Blue B, Zhang, Kun, Wilkinson, Miles F. . The Homeobox Transcription Factor RHOX10 Drives Mouse Spermatogonial Stem Cell Establishment. In Cell reports, 17, 149-164. doi:10.1016/j.celrep.2016.08.090. https://pubmed.ncbi.nlm.nih.gov/27681428/

4. Song, Hye-Won, Dann, Christina T, McCarrey, John R, Cornwall, Gail A, Wilkinson, Miles F. 2012. Dynamic expression pattern and subcellular localization of the Rhox10 homeobox transcription factor during early germ cell development. In Reproduction (Cambridge, England), 143, 611-24. doi:10.1530/REP-11-0479. https://pubmed.ncbi.nlm.nih.gov/22393026/

5. Lee, Sang-Eun, Lee, Su-Yeon, Lee, Kyung-Ah. 2013. Rhox in mammalian reproduction and development. In Clinical and experimental reproductive medicine, 40, 107-14. doi:10.5653/cerm.2013.40.3.107. https://pubmed.ncbi.nlm.nih.gov/24179867/

6. Tan, Kun, Kim, Matthew E, Song, Hye-Won, Gage, Fred H, Wilkinson, Miles F. . The Rhox gene cluster suppresses germline LINE1 transposition. In Proceedings of the National Academy of Sciences of the United States of America, 118, . doi:10.1073/pnas.2024785118. https://pubmed.ncbi.nlm.nih.gov/34083437/

7. Le Beulze, Morgane, Daubech, Cécile, Balde-Camara, Aissatu, Ghieh, Farah, Vialard, François. 2023. Mammal Reproductive Homeobox (Rhox) Genes: An Update of Their Involvement in Reproduction and Development. In Genes, 14, . doi:10.3390/genes14091685. https://pubmed.ncbi.nlm.nih.gov/37761825/