Journal
DEVELOPMENT
Volume 140, Issue 8, Pages 1751-1761Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.093641
Keywords
Wnt; Peritubular myoid cell; Spermatogenesis
Categories
Funding
- State Key Development Programs of China [2012CB910400, 2010CB945403]
- National Natural Science Foundation of China [31171318, 30930055]
- Science and Technology Commission of Shanghai Municipality [11DZ2260300]
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Peritubular myoid cells (PMCs) are myofibroblast-like cells that surround the seminiferous tubules and play essential roles in male fertility. How these cells modulate spermatogenesis and the signaling pathways that are involved are largely unknown. Here we report that Lgr4 is selectively expressed in mouse PMCs in the testes, and loss of Lgr4 leads to germ cells arresting at meiosis I and then undergoing apoptosis. In PMCs of Lgr4 mutant mice, the expression of androgen receptor, alpha-smooth muscle actin and extracellular matrix proteins was dramatically reduced. Malfunctioning PMCs further affected Sertoli cell nuclear localization and functional protein expression in Lgr4(-/-) mice. In addition, Wnt/beta-catenin signaling was activated in wild-type PMCs but attenuated in those of Lgr4(-/-) mice. When Wnt/beta-catenin signaling was reactivated by crossing with Apc(min/+) mice or by Gsk3 beta inhibitor treatment, the Lgr4 deficiency phenotype in testis was partially rescued. Together, these data demonstrate that Lgr4 signaling through Wnt/beta-catenin regulates PMCs and is essential for spermatogenesis.
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