DDB1 Regulates Sertoli Cell Proliferation and Testis Cord Remodeling by TGFβ Pathway
1
School of Life Sciences, Reproductive and Genetic Branch, Division of Life Sciences and Medicine, CAS Center for Excellence in Molecular Cell Science, University of Science and Technology of China, Hefei 230027, Anhui, China
2
Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, Anhui, China
*
Authors to whom correspondence should be addressed.
Genes 2019, 10(12), 974; https://doi.org/10.3390/genes10120974
Received: 30 October 2019
/
Accepted: 21 November 2019
/
Published: 26 November 2019
(This article belongs to the Special Issue Genomics of Sexual Development and Reproduction in Mammals)
Testis cords are the embryonic precursors of the seminiferous tubules. Development of testis cords is a key event during embryonic testicular morphogenesis and is regulated by multiple signaling molecules produced by Sertoli cells. However, the exact nature and the cascade of molecular events underlying testis cord development remain to be uncovered. In the current study, we explored the role of DNA damage binding protein 1 (DDB1) in Sertoli cells during mouse testis cord development. The genetic ablation of Ddb1 specifically in Sertoli cells resulted in the compromised Sertoli cell proliferation and disruption of testis cord remodeling in neonatal mice. This testicular dysgenesis persisted through adulthood, resulting in smaller testis and low sperm production. Mechanistically, we observed that the DDB1 degradation can stabilize SET domain-containing lysine methyltransferase 8 (SET8), which subsequently decreases the phosphorylation of SMAD2, an essential intracellular component of transforming growth factor beta (TGFβ) signaling. Taken together, our results suggest an essential role of Ddb1 in Sertoli cell proliferation and normal remodeling of testis cords via TGFβ pathway. To our knowledge, this is the first upstream regulators of TGFβ pathway in Sertoli cells, and therefore it furthers our understanding of testis cord development.
View Full-Text
Keywords:
Ddb1; Sertoli cell; testis cord; spermatogenesis; TGFβ
▼
Show Figures
Graphical abstract
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
- Supplementary File 1:
PDF-Document (PDF, 702 KiB)
MDPI and ACS Style
Zheng, W.; Nazish, J.; Wahab, F.; Khan, R.; Jiang, X.; Shi, Q. DDB1 Regulates Sertoli Cell Proliferation and Testis Cord Remodeling by TGFβ Pathway. Genes 2019, 10, 974. https://doi.org/10.3390/genes10120974
AMA Style
Zheng W, Nazish J, Wahab F, Khan R, Jiang X, Shi Q. DDB1 Regulates Sertoli Cell Proliferation and Testis Cord Remodeling by TGFβ Pathway. Genes. 2019; 10(12):974. https://doi.org/10.3390/genes10120974
Chicago/Turabian StyleZheng, Wei, Jabeen Nazish, Fazal Wahab, Ranjha Khan, Xiaohua Jiang, and Qinghua Shi. 2019. "DDB1 Regulates Sertoli Cell Proliferation and Testis Cord Remodeling by TGFβ Pathway" Genes 10, no. 12: 974. https://doi.org/10.3390/genes10120974
Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.
