Document Detail

RBPJ in mouse Sertoli cells is required for proper regulation of the testis stem cell niche.
MedLine Citation:
PMID:  25406395     Owner:  NLM     Status:  Publisher    
Stem cells are influenced by their surrounding microenvironment, or niche. In the testis, Sertoli cells are the key niche cells directing the population size and differentiation fate of spermatogonial stem cells (SSCs). Failure to properly regulate SSCs leads to infertility or germ cell hyperplasia. Several Sertoli cell-expressed genes, such as Gdnf and Cyp26b1, have been identified as being indispensable for the proper maintenance of SSCs in their niche, but the pathways that modulate their expression have not been identified. Although we have recently found that constitutively activating NOTCH signaling in Sertoli cells leads to premature differentiation of all prospermatogonia and sterility, suggesting that there is a crucial role for this pathway in the testis stem cell niche, a true physiological function of NOTCH signaling in Sertoli cells has not been demonstrated. To this end, we conditionally ablated recombination signal binding protein for immunoglobulin kappa J region (Rbpj), a crucial mediator of NOTCH signaling, in Sertoli cells using Amh-cre. Rbpj knockout mice had: significantly increased testis sizes; increased expression of niche factors, such as Gdnf and Cyp26b1; significant increases in the number of pre- and post-meiotic germ cells, including SSCs; and, in a significant proportion of mice, testicular failure and atrophy with tubule lithiasis, possibly due to these unsustainable increases in the number of germ cells. We also identified germ cells as the NOTCH ligand-expressing cells. We conclude that NOTCH signaling in Sertoli cells is required for proper regulation of the testis stem cell niche and is a potential feedback mechanism, based on germ cell input, that governs the expression of factors that control SSC proliferation and differentiation.
Thomas Xavier Garcia; Jaspreet Kaur Farmaha; Sean Kow; Marie-Claude Hofmann
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-18
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  141     ISSN:  1477-9129     ISO Abbreviation:  Development     Publication Date:  2014 Dec 
Date Detail:
Created Date:  2014-11-19     Completed Date:  -     Revised Date:  2014-11-20    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  -    
Other Details:
Languages:  ENG     Pagination:  4468-4478     Citation Subset:  -    
Copyright Information:
© 2014. Published by The Company of Biologists Ltd.
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