|

- 积分
- 1
- 威望
- 1
- 包包
- 8
|

FGF8-FGFR1 Signaling Acts as a Niche Factor for Maintaining Undifferentiated Spermatogonia in the Mouse1
' I- s3 ~; V( b. C9 T: X& @9 [+ H6 R+ K
Published online before print October 30, 2014, doi: 10.1095/biolreprod.114.1210122 t! d5 r+ h( i" j0 |2 u- I6 {
Biology of Reproduction December 1, 2014 vol. 91 no. 6 145
- V4 w4 S, u( O' m3 C, X3 ?7 {0 g/ P4 T1 w
ABSTRACT
2 Q8 t* l6 X# A* x
' C7 H& }# x; F- LIn 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.
4 K8 _, D& x7 v9 n! u+ @, ]+ T. m5 p9 s) n
Key words: developmental biology knockout model Sertoli cells signal transduction spermatogonial stem cells transgenic model1 P' l7 ^$ ]; O) F$ @
' s* I/ Y' _7 c9 y, q) o
|
-
总评分: 威望 + 1
包包 + 5
查看全部评分
|