PMID:27050391

Citation	Zhao, L, Du, X, Huang, K, Zhang, T, Teng, Z, Niu, W, Wang, C and Xia, G (2016) Rac1 modulates the formation of primordial follicles by facilitating STAT3-directed Jagged1, GDF9 and BMP15 transcription in mice. Sci Rep 6:23972
Abstract	The size of the primordial follicle pool determines the reproductive potential of mammalian females, and establishment of the pool is highly dependent on specific genes expression. However, the molecular mechanisms by which the essential genes are regulated coordinately to ensure primordial follicle assembly remain a mystery. Here, we show that the small GTPase Rac1 plays an indispensable role in controlling the formation of primordial follicles in mouse ovary. Employing fetal mouse ovary organ culture system, we demonstrate that disruption of Rac1 retarded the breakdown of germline cell cysts while Rac1 overexpression accelerated the formation of primordial follicles. In addition, in vivo inhibitor injection resulted in the formation of multi-oocyte follicles. Subsequent investigation showed that Rac1 induced nuclear import of STAT3 by physical binding. In turn, nuclear STAT3 directly activated the transcription of essential oocyte-specific genes, including Jagged1, GDF9, BMP15 and Nobox. Further, GDF9 and BMP15 regulated the translation of Notch2 via mTORC1 activation in pregranulosa cells. Overexression or addition of Jagged1, GDF9 and BMP15 not only reversed the effect of Rac1 disruption, but also accelerated primordial follicle formation via Notch2 signaling activation. Collectively, these results indicate that Rac1 plays important roles as a key regulator in follicular assembly.
Links	PubMed Online version:10.1038/srep23972
Keywords
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:RAC1		GO:0007262: STAT protein import into nucleus	ECO:0000315:		P		Figure 5B showed a decrease in p-STAT3 at tyrosine 705 ( with present of Rac inhibitor) compared to the control and Figure 5C showed a decrease in staining around the nuclear when Rac- specific inhibitor was presented. aka inhibition of Rac resulted in less phosphorylated STAT3 or down-regulated nuclear import. So Rac1 regulates STAT3 activity by affecting nuclear STAT3 phosphorylation level	complete CACAO 11576
MOUSE:RAC1		GO:2000386: positive regulation of ovarian follicle development	ECO:0000315:		P		Figure 1E,F	complete CACAO 11578
MOUSE:RAC1		GO:0043073: germ cell nucleus	ECO:0000314:		C		Figure 1A shows immunostaining of Rac1 in the nucleus of germ cells.	complete CACAO 11582
MOUSE:STAT3		GO:0005634: nucleus	ECO:0000314:		C		Figure 5C shows immunostaining of STAT3 in the nucleus.	complete CACAO 11580
HUMAN:STAT3		GO:0045944: positive regulation of transcription from RNA polymerase II promoter	ECO:0000314:		P		Figure 4, and from text " collectively, these results suggest that STAT3 directly targets and activates transcription of oocyte-specific genes."	complete CACAO 11579

References

See Help:References for how to manage references in GONUTS.