Polycomb function during oogenesis is required for mouse embryonic development

Pósfai, Eszter; Kunzmann, Rico; Brochard, Vincent; Salvaing, Juliette; Cabuy, Erik; Roloff, Tim; Liu, Zichuan; Tardat, Mathieu; Lohuizen, Maarten van; Vidal, Miguel; Beaujean, Nathalie; Peters, Antoine H.F.M.

doi:10.1101/gad.188094.112

Cited by 120 publications

(110 citation statements)

References 62 publications

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“…Although the complexity of these changes is just beginning to be understood, it is well known that this process is indispensable for ensuring normal embryo development. This is demonstrated by experiments where mutation of histonemodifying enzymes or Dnmt in embryos leads to severe abnormalities or death (Li et al 1992;Peters et al 2001;Posfai et al 2012). This indicates that remodelling during early stages of development is of critical importance for resetting the epigenome in preparation for establishment of new programs of differentiation during lineage commitment.…”

Section: Recent Advances In Epigeneticsmentioning

confidence: 89%

Epigenetics and developmental programming of welfare and production traits in farm animals

Sinclair

Rutherford

Wallace

et al. 2016

Reprod. Fertil. Dev.

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Abstract. The concept that postnatal health and development can be influenced by events that occur in utero originated from epidemiological studies in humans supported by numerous mechanistic (including epigenetic) studies in a variety of model species. Referred to as the 'developmental origins of health and disease' or 'DOHaD' hypothesis, the primary focus of large-animal studies until quite recently had been biomedical. Attention has since turned towards traits of commercial importance in farm animals. Herein we review the evidence that prenatal risk factors, including suboptimal parental nutrition, gestational stress, exposure to environmental chemicals and advanced breeding technologies, can determine traits such as postnatal growth, feed efficiency, milk yield, carcass composition, animal welfare and reproductive potential. We consider the role of epigenetic and cytoplasmic mechanisms of inheritance, and discuss implications for livestock production and future research endeavours. We conclude that although the concept is proven for several traits, issues relating to effect size, and hence commercial importance, remain. Studies have also invariably been conducted under controlled experimental conditions, frequently assessing single risk factors, thereby limiting their translational value for livestock production. We propose concerted international research efforts that consider multiple, concurrent stressors to better represent effects of contemporary animal production systems.

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Section: Recent Advances In Epigeneticsmentioning

confidence: 89%

Epigenetics and developmental programming of welfare and production traits in farm animals

Sinclair

Rutherford

Wallace

et al. 2016

Reprod. Fertil. Dev.

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“…Whereas Porcn transcript is detectable at increasing levels from the 2-cell to the morula stage and at low levels in blastocysts (Casanova et al, 2012;Hamatani et al, 2004;Xie et al, 2010), it is undetectable in oocytes (Macfarlan et al, 2012;Posfai et al, 2012), suggesting that rescue by maternal protein is unlikely to explain the absence of any early embryo defects in Porcn zygotic mutants. In order to test this more directly, we generated Porcn lox/lox ; Zp3-Cre +/tg females that delete Porcn in the developing oocytes (Lewandoski et al, 1997) and crossed them to wild-type males carrying an X-linked EGFP transgene (Hadjantonakis et al, 1998 ) male embryos are not.…”

Section: Porcn-mediated Wnt Signaling Is Not Required Prior To Gastrumentioning

confidence: 99%

Porcn-dependent Wnt signaling is not required prior to mouse gastrulation

et al. 2013

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SUMMARYIn mice and humans the X-chromosomal porcupine homolog (Porcn) gene is required for the acylation and secretion of all 19 Wnt ligands and thus represents a bottleneck for all Wnt signaling. We have generated a mouse line carrying a floxed allele for Porcn and used zygotic, oocyte-specific and visceral endoderm-specific deletions to investigate embryonic and extra-embryonic requirements for Wnt ligand secretion. We show that there is no requirement for Porcn-dependent secretion of Wnt ligands during preimplantation development of the mouse embryo. Porcn-dependent Wnts are first required for the initiation of gastrulation, where Porcn function is required in the epiblast but not the visceral endoderm. Heterozygous female embryos, which are mutant in both trophoblast and visceral endoderm due to imprinted X chromosome inactivation, complete gastrulation but display chorio-allantoic fusion defects similar to Wnt7b mutants. Our studies highlight the importance of Wnt3 and Wnt7b for embryonic and placental development but suggest that endogenous Porcn-dependent Wnt secretion does not play an essential role in either implantation or blastocyst lineage specification.

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“…In addition to DNA damage checkpoints, malfunction of zygotic genome activation (ZGA) also causes two-cell stage arrest (Bultman et al, 2006;Posfai et al, 2012;Wu et al, 2003). When the expression of ZGA genes (Zeng et al, 2004;Zeng and Schultz, 2005) was examined by quantitative RT-PCR, the mRNA levels of ZGA genes such as Tdpoz1, Tdpoz3, Tdpoz4 increased.…”

Section: Dna Damage Repair Is Defective In Bcas2 Mnull Early Embryosmentioning

confidence: 99%

Maternal BCAS2 protects genomic integrity in mouse early embryonic development

Wang

Xiang

et al. 2015

Development

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Mammalian early embryos maintain accurate genome integrity for proper development within a programmed timeline despite constant assaults on their DNA by replication, DNA demethylation and genetic defects transmitted from germ cells. However, how genome integrity is safeguarded during mammalian early embryonic development remains unclear. BCAS2 (breast carcinoma amplified sequence 2), a core component of the PRP19 complex involved in pre-mRNA splicing, plays an important role in the DNA damage response through the RPA complex, a key regulator in the maintenance of genome integrity. Currently, the physiological role of BCAS2 in mammals is unknown. We now report that BCAS2 responds to endogenous and exogenous DNA damage in mouse zygotes. Maternal depletion of BCAS2 compromises the DNA damage response in early embryos, leading to developmental arrest at the two-to four-cell stage accompanied by the accumulation of damaged DNA and micronuclei. Furthermore, BCAS2 mutants that are unable to bind RPA1 fail in DNA repair during the zygotic stage. In addition, phosphorylated RPA2 cannot localise to the DNA damage sites in mouse zygotes with disrupted maternal BCAS2. These data suggest that BCAS2 might function through the RPA complex during DNA repair in zygotes. Together, our results reveal that maternal BCAS2 maintains the genome integrity of early embryos and is essential for female mouse fertility.

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Polycomb function during oogenesis is required for mouse embryonic development

Cited by 120 publications

References 62 publications

Epigenetics and developmental programming of welfare and production traits in farm animals

Epigenetics and developmental programming of welfare and production traits in farm animals

Porcn-dependent Wnt signaling is not required prior to mouse gastrulation

Maternal BCAS2 protects genomic integrity in mouse early embryonic development

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