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Biol Reprod. 2014 Dec;91(6):145. doi: 10.1095/biolreprod.114.121012. Epub 2014 Oct 30.

FGF8-FGFR1 signaling acts as a niche factor for maintaining undifferentiated spermatogonia in the mouse.

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Division of Mammalian Development, National Institute of Genetics, Mishima, Shizuoka, Japan.
Division of Mammalian Development, National Institute of Genetics, Mishima, Shizuoka, Japan Department of Genetics, Sokendai, Mishima, Shizuoka, Japan


In mammalian testes, spermatogonial stem cells (SSCs) maintain spermatogenesis over a long period of time by undergoing self-renewal and differentiation. SSCs are among the most primitive of spermatogenic cells (undifferentiated spermatogonia), and their activities are strictly regulated by extrinsic niche factors. However, the factors that constitute a testicular niche remain poorly understood. In this study, we demonstrate that fibroblast growth factor (FGF) signaling maintains undifferentiated spermatogonia through activating ERK1/2 signaling in vivo. Undifferentiated spermatogonia comprise GFRA1(+) and NANOS3(+) subpopulations, which are likely to undergo self-renewal and enter the differentiation pathway, respectively. In the testis, Fgfr1 was expressed in the entire population of undifferentiated spermatogonia, and deleting FGFR1 in spermatogenic cells partially inactivated ERK1/2 and resulted in reduced numbers of both GFRA1(+) and NANOS3(+) cells. In addition, Fgf8 was expressed in spermatogenic cells, and loss- and gain-of-function models of FGF8 demonstrated that FGF8 positively regulated the numbers of undifferentiated spermatogonia through FGFR1, particularly among NANOS3(+) cells. Finally we show a possible involvement of FGF signaling in the reversion from NANOS3(+) into GFRA1(+) undifferentiated spermatogonia. Taken together, our data suggest that FGF signaling is an important component of the testicular niche and has a unique function for maintaining undifferentiated spermatogonia.


Sertoli cells; developmental biology; knockout model; signal transduction; spermatogonial stem cells; transgenic model

[Indexed for MEDLINE]

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