- 积分
- 1
- 威望
- 1
- 包包
- 8
|
FGF8-FGFR1 Signaling Acts as a Niche Factor for Maintaining Undifferentiated Spermatogonia in the Mouse19 [8 ]# ?1 C; r6 y6 T$ V1 a9 T1 Z- |
( L- V5 p0 M' |, ~, dPublished online before print October 30, 2014, doi: 10.1095/biolreprod.114.121012% K5 \; e0 M6 k# [$ a1 D' s
Biology of Reproduction December 1, 2014 vol. 91 no. 6 145$ s# o u! O5 H' i
5 l& t/ S) a: X* e
ABSTRACT
! Z% n1 I3 o8 p! o- Z; ^8 i+ r6 G: r1 }$ r
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.
. a7 _/ Q8 |7 u! Y# h
" q7 c. g+ Y, X& _! m4 W: x+ YKey words: developmental biology knockout model Sertoli cells signal transduction spermatogonial stem cells transgenic model
' o$ {7 B" H: H8 q, V0 m" |& m4 o
4 L a. \5 h& M. D |
-
总评分: 威望 + 1
包包 + 5
查看全部评分
|