Differential Oocyte-Specific Expression of Cre Recombinase Activity in GDF-9-iCre, Zp3cre, and Msx2Cre Transgenic Mice1

Lan, Zi-Jian; Xu, Xueping; Cooney, Austin J.

doi:10.1095/biolreprod.104.031757

Cited by 233 publications

(268 citation statements)

References 31 publications

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“…Oocyte-specific knockouts of Tsc1 or Pten (a negative regulator of PI3K signaling) undergo normal primordial follicle formation (Reddy et al 2008, Adhikari et al 2010. However, in these studies, the Gdf9 promoter was used to drive Cre recombinase in oocytes, and this promoter is not active until PND3 after most cysts have already broken down (Lan et al 2004). Therefore, more work is needed to determine the effects of the PI3K pathway in cyst breakdown.…”

Section: Growth Factors and Signaling Moleculesmentioning

confidence: 99%

Follicular assembly: mechanisms of action

Pepling¹

2012

Reproduction

211

190

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The differentiation of primordial germ cells (PGCs) into functional oocytes is important for the continuation of species. In mammals, PGCs begin to differentiate into oocytes during embryonic development. Oocytes develop in clusters called germ line cysts. During fetal or neonatal development, germ cell cysts break apart into single oocytes that become surrounded by pregranulosa cells to form primordial follicles. During the process of cyst breakdown, a subset of cells in each cyst undergoes cell death with only one-third of the initial number of oocytes surviving to form primordial follicles. The mechanisms that control cyst breakdown, oocyte survival, and follicle assembly are currently under investigation. This review describes the mechanisms that have been implicated in the control of primordial follicle formation, which include programmed cell death regulation, growth factor and other signaling pathways, regulation by transcription factors and hormones, meiotic progression, and changes in cell adhesion. Elucidation of mechanisms leading to formation of the primordial follicle pool will help research efforts in ovarian biology and improve treatments of female infertility, premature ovarian failure, and reproductive cancers.

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Section: Growth Factors and Signaling Moleculesmentioning

confidence: 99%

Follicular assembly: mechanisms of action

Pepling¹

2012

Reproduction

211

190

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“…We crossed mice in which the Dcr gene was floxed around exon 24, encoding most of the second RNAse III domain ( Figure 7A; provided by Harfe et al, 2005), with transgenic mice in which the Cre-recombinase is under the control of the growth and differentiation factor-9 (gdf-9) promoter and thus exclusively expressed in oocytes of primordial and later stage follicles (Lan et al, 2004). Early inactivation of dicer should lead to the total depletion of small RNAs in fully grown oocytes.…”

Section: Depletion Of Small Rnas Only Marginally Decreases Small Egfpmentioning

confidence: 99%

“…Dcr flox (Dcr fx ) and Gdf9Cre mice were kindly provided by B. Harfe (University of Florida College of Medicine, Gainesville, FL) and A. J. Cooney (Baylor College of Medicine, Houston, TX), respectively, and were genotyped as described in Harfe et al (2005), Lecureuil et al (2002), and Lan et al (2004). To achieve selective inactivation of Dcr in oocytes, we intercrossed transgenic Gdf9Cre mice expressing Cre recombinase under the control of the Gdf9 gene promoter with mice carrying two floxed Dcr alleles in order to generate Dcr fx/fx ;Gfd9Cre mice lacking Dcr in primordial/primary oocytes.…”

Section: Transgenic Micementioning

confidence: 99%

Dcp1-Bodies in Mouse Oocytes

Swetloff

Conne

Huarte

et al. 2009

MBoC

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Processing bodies (P-bodies) are cytoplasmic granules involved in the storage and degradation of mRNAs. In somatic cells, their formation involves miRNA-mediated mRNA silencing. Many P-body protein components are also found in germ cell granules, such as in mammalian spermatocytes. In fully grown mammalian oocytes, where changes in gene expression depend entirely on translational control, RNA granules have not as yet been characterized. Here we show the presence of P-body-like foci in mouse oocytes, as revealed by the presence of Dcp1a and the colocalization of RNAassociated protein 55 (RAP55) and the DEAD box RNA helicase Rck/p54, two proteins associated with P-bodies and translational control. These P-body-like structures have been called Dcp1-bodies and in meiotically arrested primary oocytes, two types can be distinguished based on their size. They also have different protein partners and sensitivities to the depletion of endogenous siRNA/miRNA and translational inhibitors. However, both type progressively disappear during in vitro meiotic maturation and are virtually absent in metaphase II-arrested secondary oocytes. Moreover, this disassembly of hDcp1a-bodies is concomitant with the posttranslational modification of EGFP-hDcp1a. INTRODUCTIONGene expression flows from DNA to protein using mRNA as an intermediate. Transcripts can either be used immediately as template for protein synthesis or translationally silenced and stored for later translation. A subset of silenced mRNAs is packaged into microscopically visible RNP granules that lack a limiting lipid membrane (Kedersha and Anderson, 2007). In mammals, processing bodies (P-bodies) RNA granules are present in a broad range of somatic cell types, including highly specialized cells such as neurons. Initially, P-bodies were discovered as 5Ј-3Ј mRNA decay centers in mammalian somatic cells (Bashkirov et al., 1997;Eystathioy et al., 2003;Cougot et al., 2004), and were found to be conserved in yeast (Sheth and Parker, 2003); because of the systematic localization of the decapping protein Dcp1a in P-bodies, they were also called Dcp1-bodies. Subsequently, P-bodies were shown to be involved in mRNA surveillance (Chen and Shyu, 2003;Couttet and Grange, 2004), RNAmediated silencing (Rehwinkel et al., 2005;Jakymiw et al., 2005;Liu et al., 2005a), and translational control Liu et al., 2005b;Bhattacharyya et al., 2006b).A role for P-bodies in translational control was first highlighted in yeast cells. It was shown that the entry of an mRNA into P-bodies does not automatically lead to its degradation: upon glucose starvation mRNAs can be temporarily stored in P-bodies, which increase in size and number, and then exit the foci upon refeeding to reenter polysomes (Brengues et al., 2005). In mammals, this reversibility of mRNA localization has been observed for miRNA-mediated mRNA repression in Huh7 cells (Pillai, 2005;Pillai et al., 2005;Bhattacharyya et al., 2006a). Although such a shuttling of mRNAs between polysomes and P-bodies has not been described for other mecha...

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“…Our current study provides conclusive evidence that the initial oocyte pool is the only source of fertility throughout reproductive life in mammals. transgenic mice are highly efficient in targeting oocytes of the entire follicle pool (14,15). Importantly, Gdf9 is not expressed in reported putative GSCs in postnatal mouse ovaries (4), making the Gdf9-Cre mouse model ideal for targeting oocytes but not the proposed GSCs.…”

Section: Resultsmentioning

confidence: 99%

“…The Gdf9-Cre;iDTR oocyte-ablation mouse model was generated by crossing the iDTR knock-in females (007900, Jackson Laboratory) with Gdf9-Cre transgenic males (14,15). In this mouse strain, the Cre recombinase removes the STOP sequence that is flanked by two loxP sites in the iDTR allele and allows for the expression of simian DTR in the oocytes of all of the follicles in the ovary from the primordial to the antral stages.…”

Section: Methodsmentioning

confidence: 99%

Life-long in vivo cell-lineage tracing shows that no oogenesis originates from putative germline stem cells in adult mice

Zhang

Liu

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Whether or not oocyte regeneration occurs in adult life has been the subject of much debate. In this study, we have traced germcell lineages over the life spans of three genetically modified mouse models and provide direct evidence that oogenesis does not originate from any germline stem cells (GSCs) in adult mice. By selective ablation of all existing oocytes in a Gdf9-Cre;iDTR mouse model, we have demonstrated that no new germ cells were ever regenerated under pathological conditions. By in vivo tracing of oocytes and follicles in the Sohlh1-CreER T2 ;R26R and Foxl2-CreER T2 ;mT/mG mouse models, respectively, we have shown that the initial pool of oocytes is the only source of germ cells throughout the life span of the mice and that no adult oogenesis ever occurs under physiological conditions. Our findings clearly show that there are no GSCs that contribute to adult oogenesis in mice and that the initial pool of oocytes formed in early life is the only source of germ cells throughout the entire reproductive life span.genetically modified mouse models | oocyte tracing | follicle tracing | life-long observations | no postnatal oocyte regeneration

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Differential Oocyte-Specific Expression of Cre Recombinase Activity in GDF-9-iCre, Zp3cre, and Msx2Cre Transgenic Mice1

Cited by 233 publications

References 31 publications

Follicular assembly: mechanisms of action

Follicular assembly: mechanisms of action

Dcp1-Bodies in Mouse Oocytes

Life-long in vivo cell-lineage tracing shows that no oogenesis originates from putative germline stem cells in adult mice

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