In germ cells of mouse embryonic ovaries, the decision to enter meiosis precedes premeiotic DNA replication

Baltus, Andrew E.; Menke, Douglas B.; Hu, Yueh Chiang; Goodheart, Mary L.; Carpenter, Anne E.; Rooij, Dirk G. de; Page, David C.

doi:10.1038/ng1919

Cited by 473 publications

(574 citation statements)

References 29 publications

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“…In budding yeast, nutrient deprivation causes cell cycle arrest and entry into meiosis in the G1 phase (Honigberg and Purnapatre, 2003), while in the mouse fetal ovary, loss of the meiosis promoting gene Stra8 leads to germ cells arrested with a 2n DNA content (Baltus et al, 2006). These and other results suggest that the decision to enter meiosis may generally occur prior to meiotic S phase.…”

Section: Research Articlementioning

confidence: 87%

Cyclin E and CDK-2 regulate proliferative cell fate and cell cycle progression in the C. elegans germline

et al. 2011

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SUMMARYThe C. elegans germline provides an excellent model for analyzing the regulation of stem cell activity and the decision to differentiate and undergo meiotic development. The distal end of the adult hermaphrodite germline contains the proliferative zone, which includes a population of mitotically cycling cells and cells in meiotic S phase, followed by entry into meiotic prophase. The proliferative fate is specified by somatic distal tip cell (DTC) niche-germline GLP-1 Notch signaling through repression of the redundant GLD-1 and GLD-2 pathways that promote entry into meiosis. Here, we describe characteristics of the proliferative zone, including cell cycle kinetics and population dynamics, as well as the role of specific cell cycle factors in both cell cycle progression and the decision between the proliferative and meiotic cell fate. Mitotic cell cycle progression occurs rapidly, continuously, with little or no time spent in G1, and with cyclin E (CYE-1) levels and activity high throughout the cell cycle. In addition to driving mitotic cell cycle progression, CYE-1 and CDK-2 also play an important role in proliferative fate specification. Genetic analysis indicates that CYE-1/CDK-2 promotes the proliferative fate downstream or in parallel to the GLD-1 and GLD-2 pathways, and is important under conditions of reduced GLP-1 signaling, possibly corresponding to mitotically cycling proliferative zone cells that are displaced from the DTC niche. Furthermore, we find that GLP-1 signaling regulates a third pathway, in addition to the GLD-1 and GLD-2 pathways and also independent of CYE-1/CDK-2, to promote the proliferative fate/inhibit meiotic entry.

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Section: Research Articlementioning

confidence: 87%

Cyclin E and CDK-2 regulate proliferative cell fate and cell cycle progression in the C. elegans germline

et al. 2011

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“…43 Presumably, during these Kit-mediated mitotic divisions, accumulation of key factors required for meiosis occur. One of these factors is certainly Stra8, which has been proposed to be essential for the last round of pre-meiotic DNA synthesis in female fetal germ cells, 6 and to regulate the switch from a mitotic pattern of cell division to the meiotic pattern in postnatal male germ cells. 15,16 In conclusion, we propose a model (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…10,12 It has been recently shown that RA produced by mesonephroi causes entry into meiosis of germ cells in the ovary, while its effect is prevented in the fetal testis by the action of the retinoid-degrading enzyme CYP26B1. 13,14 It has been proposed that a critical role in inducing meiosis in both female and male 6,15,16 is played by the RA-stimulated Stra8 gene; however it remains to be elucidated if RA regulates other meiosis promoting genes and which are the precise mechanisms that orchestrate meiotic entry in the postnatal testis.…”

Section: Introductionmentioning

confidence: 99%

“…5 These animals are sterile because the seminiferous tubules contain only undifferentiated Kit negative spermatogonia, indicating a role of vitamin A in spermatogonia differentiation. 5 More recently it has been shown that the vitamin A derivative retinoic acid (RA) (either as all-trans or as 9-cis retinoic acid) promotes the expression of Stimulated by Retinoic Acid Gene 8 (Stra8), a key regulator of mammalian meiosis, 6 and Kit expression in undifferentiated spermatogonia. 7,8 RA functions inside the nucleus recognising two different classes of retinoid receptors.…”

Section: Introductionmentioning

confidence: 99%

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ATRA and KL promote differentiation toward the meiotic program of male germ cells.

Pellegrini¹,

Filipponi²,

Gori³

et al. 2008

Cell Cycle

112

144

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While it is known that Retinoic Acid (RA) induces meiosis in mouse female fetal gonads, the mechanisms which regulate this process during spermatogenesis are poorly understood. We show that the All trans RA derivative (ATRA) and Kit Ligand (KL) increase meiotic entry of postnatal mouse spermatogonia in vitro without synergism. Competence to enter meiosis is reached by spermatogonia only at the stage in which they undergo Kit-dependent divisions. Besides increasing Kit expression in spermatogonia, ATRA also upregulates KL expression in Sertoli cells. Both ATRA and KL increase the expression of Stimulated by Retinoic Acid Gene 8 and Dmc1, an early meiotic marker. A specific Kit tyrosine kinase inhibitor prevents the increase in the number of meiotic cells induced by both the two factors, suggesting that they converge on common Kit-dependent signalling pathways. Meiotic entry induced by ATRA and KL is independent from their ability to affect germ cell viability, and is mediated by the activation of PI3K and MAPK pathways through Kit autophosphorylation. ATRA-induced phosphorylation of the two downstream kinases is mediated by a non-genomic mechanism.These data suggest that RA may control the timing of meiosis by influencing both the somatic and the germ cell compartment of the postnatal testis through the activation of the KL/Kit system.

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“…Meiotic entry in both sexes requires the HLH protein Stimulated by Retinoic Acid gene 8 (STRA8). 102,103 In females, Stra8 is expressed in germ cells in response to retinoic acid (RA) beginning at E12.5-13.5, and meiotic prophase begins soon afterward. 104 In prenatal males, the cytochrome P450 enzyme CYP26B1 degrades retinoic acid, preventing induction of Stra8.…”

Section: Meiotic Initiation and Germ Cell Sex Determinationmentioning

confidence: 99%

Genetics of germ cell development

2012

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| The germ line represents a continuous cellular link between generations and between species, but the germ cells themselves develop in a specialized, organism-specific context. The three most common animal model organisms, C. elegans, Drosophila, and mouse, display striking similarities as well as major differences in the means by which they control germ cell development.Comparison of the germ cells of these three organisms sheds light not only on universal aspects of germline regulation, but also on control of the pluripotent state in vivo and on the earliest steps of embryogenesis. Taking a broad perspective, we will follow the germ cells from specification in the early embryo, through gametogenesis, to fertilization, and highlight themes from the comparison of three alternative strategies for navigating the fundamental cycle of sexual reproduction.

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In germ cells of mouse embryonic ovaries, the decision to enter meiosis precedes premeiotic DNA replication

Cited by 473 publications

References 29 publications

Cyclin E and CDK-2 regulate proliferative cell fate and cell cycle progression in the C. elegans germline

Cyclin E and CDK-2 regulate proliferative cell fate and cell cycle progression in the C. elegans germline

ATRA and KL promote differentiation toward the meiotic program of male germ cells.

Genetics of germ cell development

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