Genetics and Proteomics of Mouse Egg Activation
小鼠卵子激活的遗传学和蛋白质组学
基本信息
- 批准号:10366090
- 负责人:
- 金额:$ 23.46万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-03-15 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:AffectAnimalsAssisted Reproductive TechnologyBiochemicalBiological MarkersBiological ModelsCalciumCalcium SignalingCell CycleCell Differentiation processCell NucleusCellsChemicalsDataDepositionDetectionDevelopmentDiagnosisDiseaseDrosophila genusEmbryoEmbryonic DevelopmentEnzymesEventFailureFertilityFertilizationFertilization in VitroFutureGene ExpressionGene ProteinsGeneticGenetic TranscriptionGenetic studyGenomeHumanInfertilityInvertebratesIonophoresMammalsMaternal Messenger RNAMediatingMeiosisMembraneMetaphaseMethodologyModelingModificationMolecularMolecular GeneticsMonitorMusNatureNucleic AcidsOocytesOogenesisOrganismPathway interactionsPhosphorylationPhosphotransferasesPlacentaPost-Translational Protein ProcessingProceduresProcessProductionProtein IsoformsProteinsProteomeProteomicsRanaReportingRoleSea UrchinsSterilityStrontiumTestingTotipotentTranslationsanalytical toolbasecalmodulin-dependent protein kinase IIdiagnostic tooleggfemale fertilitymacromoleculemenphosphoproteomicsprotein expressionsperm celltooltranscriptometranslation factorzygote
项目摘要
PROJECT SUMMARY/ABSTRACT
Ovulated human and mouse oocytes are stalled in meiosis II. They are transcriptionally quiescent but have
a maternally-loaded transcriptome and proteome. Fertilization triggers “egg activation”, in which a rise(s) of
calcium in the oocyte induces several key events that allow transition to embryonic development, namely,
meiotic resumption and completion, changes to the egg’s proteome, and genome activation after the first
zygotic division. Therefore, egg activation is required for the oocyte to become a totipotent zygote. Despite the
essential nature of this process for female fertility, the molecular events of egg activation are not well
understood, primarily for technical reasons. Egg activation occurs without new transcription; thus nucleic acids-
based ‘omics comparisons are uninformative. The macromolecules that transduce the calcium signal to effect
downstream cellular events are not known in humans or any other mammal.
Recent studies in MW’s lab exploited technical advantages of the Drosophila model system to show that
there is large phospho-modulation of the maternally-provided proteome during egg activation (this also occurs
in frogs and sea urchins). We hypothesized, and our genetic data supported, that this posttranslational
modification regulated the activity of stored proteins to permit transition of an arrested mature oocyte to a cell
that can undertake embryogenesis. We then showed that a calcium-regulated phospho-regulatory enzyme
mediates these phospho-changes in the cell cycle machinery, translation factors and other proteins needed to
transition the egg to an embryo.
In this R21 we propose to test this model for mammalian oocytes, using mouse as a model. Following
procedures analogous to those used for Drosophila, we will determine whether there are phosphoproteome
changes during mouse egg activation, and which proteins undergo these changes. We will then test the role of
CamKII, a calcium-regulated kinase that has been shown to be required for egg activation in mouse, in making
these phospho-changes.
The results of our studies will lay the groundwork for the field in several ways, including developing
phosphoproteomics for mouse oocytes and determining proteins that are phospho-regulated during egg
activation. The results will provide information essential for future studies into the roles of the regulated
proteins that we identify here, and the effects of specific phosphomodulations during this critical developmental
transition. Such fundamental studies will be important for identifying the molecular and genetic bases of human
infertilities associated with defective egg activation, providing biomarkers to monitor this process, and
potentially for optimizing conditions for assisted reproductive technologies.
项目总结/文摘
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Cilia take the egg on a magic carpet ride.
纤毛带着鸡蛋乘坐魔毯。
- DOI:10.1073/pnas.2108887118
- 发表时间:2021
- 期刊:
- 影响因子:11.1
- 作者:Suarez,SusanS;Wolfner,MarianaF
- 通讯作者:Wolfner,MarianaF
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John C Schimenti其他文献
Monoallelic gene expression in mice: who? When? How? Why?
小鼠中的单等位基因表达:谁?
- DOI:
10.1101/gr.215601 - 发表时间:
2001 - 期刊:
- 影响因子:7
- 作者:
John C Schimenti - 通讯作者:
John C Schimenti
Mice and the role of unequal recombination in gene-family evolution.
小鼠和不等重组在基因家族进化中的作用。
- DOI:
10.1086/302220 - 发表时间:
1999 - 期刊:
- 影响因子:9.8
- 作者:
John C Schimenti - 通讯作者:
John C Schimenti
John C Schimenti的其他文献
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{{ truncateString('John C Schimenti', 18)}}的其他基金
Mechanisms underlying sex-dependent pregnancy outcomes caused by fetal and maternal genomic instability
胎儿和母体基因组不稳定引起的性别依赖性妊娠结局的机制
- 批准号:
10391992 - 财政年份:2022
- 资助金额:
$ 23.46万 - 项目类别:
Mechanisms underlying sex-dependent pregnancy outcomes caused by fetal and maternal genomic instability
胎儿和母体基因组不稳定引起的性别依赖性妊娠结局的机制
- 批准号:
10704495 - 财政年份:2022
- 资助金额:
$ 23.46万 - 项目类别:
Genetics and Proteomics of Mouse Egg Activation
小鼠卵子激活的遗传学和蛋白质组学
- 批准号:
10209649 - 财政年份:2021
- 资助金额:
$ 23.46万 - 项目类别:
Epigenetics and Genetics of Infertility and Associated Comorbidities
不孕症及相关合并症的表观遗传学和遗传学
- 批准号:
10613343 - 财政年份:2019
- 资助金额:
$ 23.46万 - 项目类别:
Epigenetics and Genetics of Infertility and Associated Comorbidities
不孕症及相关合并症的表观遗传学和遗传学
- 批准号:
10379349 - 财政年份:2019
- 资助金额:
$ 23.46万 - 项目类别:
GENDER BIAS IN MAMMALIAN DNA REPLICATION DURING DEVELOPMENT
发育过程中哺乳动物 DNA 复制的性别偏见
- 批准号:
9407791 - 财政年份:2017
- 资助金额:
$ 23.46万 - 项目类别:
Identification and Functional Validation of Human Infertility Alleles
人类不育等位基因的鉴定和功能验证
- 批准号:
10385752 - 财政年份:2015
- 资助金额:
$ 23.46万 - 项目类别:
Identification and Functional Validation of Human Infertility Alleles
人类不育等位基因的鉴定和功能验证
- 批准号:
8973021 - 财政年份:2015
- 资助金额:
$ 23.46万 - 项目类别:
Identification and Functional Validation of Human Infertility Alleles
人类不育等位基因的鉴定和功能验证
- 批准号:
10224949 - 财政年份:2015
- 资助金额:
$ 23.46万 - 项目类别:
Identification and Functional Validation of Human Infertility Alleles
人类不育等位基因的鉴定和功能验证
- 批准号:
10616671 - 财政年份:2015
- 资助金额:
$ 23.46万 - 项目类别:
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