Variation in maternal and zygotic control of embryogenesis events in Drosophila

果蝇胚胎发生事件的母体和合子控制的变化

• 批准号: 7989474
• 负责人: CEDRIC S WESLEY
• 金额: $ 18.56万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-21 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7989474
• 关键词: Adopted; Adoption; Affect; Alleles; Animal Model; Assisted Reproductive Technology; Biological Process; Cell Differentiation process; Cells; Code; Commit; Complex; Consensus; Defect; Development; Disease; Drosophila genus; Drosophila melanogaster; Embryo; Embryonic Development; Environmental Risk Factor; Event; Evolution; Fetal Development; Foundations; Genes; Genetic; Genome; Germ Cells; Goals; Human; Instinct; Length; Maternal Messenger RNA; Messenger RNA; Methods; Molecular; Molecular Genetics; Molecular Profiling; Mothers; Notch Signaling Pathway; Nuclear Export; Organism; Outcome; Pathway interactions; Pattern; Poly A; Polyadenylation; Population; Pregnancy; Process; Regulation; Resistance; Sampling; Signal Transduction; Signaling Pathway Gene; Site; Somatic Cell; Specific qualifier value; Techniques; Testing; Translations; Untranslated Regions; Variant; analytical method; analytical tool; autism spectrum disorder; base; cell behavior; cell fate specification; design; developmental genetics; early onset; expectation; meetings; notch protein; offspring; public health relevance; research study; stem cell differentiation; stem cell technology; success; tool; zygote

DESCRIPTION (provided by applicant): Preliminary studies in the model organism Drosophila melanogaster provide evidence for developmental variation due to interplay between the mother and the zygote (offspring) for the control of early events in embryogenesis. This interplay could to be based on zygotic resistance to maternal enforcement of Notch signaling in order to restrict the opportunity for zygotic cells to become germ cells. From a Darwinian perspective the germ cell would be the default fate. Activation of Notch signaling would promote adoption of the alternate somatic cell fate on which development depends. The mother and the zygote appear to use mRNA 3' UTR based mechanisms to regulate interplay. The goal of experiments described in this R21 proposal is to test for evidence of mother-zygote interplay. This goal will be achieved by testing the hypothesis that the mother and the zygote dynamically control Notch signaling in early embryogenesis events through sequences in the 3' UTR of mRNAs. Experiments are designed under three specific aims: (1) use the power of Drosophila genetics to test predictions from mother-zygote interplay in germ cell-somatic cell fate specification and three other early embryogenesis events; (2) use SNPs and molecular methods on wild type and genetically manipulated embryos to test predictions of changes in the expression profile of a sample of Notch pathway genes when their maternal or the zygotic component is removed; and (3) use an analytical method to determine if the sample of Notch pathway genes manifest patterns of sequence variation in the 3' UTR predicted from mother-offspring interplay. Early embryogenesis events can affect development more profoundly than later events and the Notch pathway functions are similar in all developmental events. Thus, mother-offspring interplay has the potential to impact a wide range of biological processes including cell fate specification, complex developmental diseases, regulation of stem cell differentiation, and assisted reproductive technology- based human pregnancy. A message that might emerge for this study is that in order to fully understand these processes it might be necessary to adapt game theoretic analysis and other analytical tools developed by population and evolutionary biologists. PUBLIC HEALTH RELEVANCE: Interaction between products of the maternal and zygotic genomes when they first meet could control many aspects of early fetal development. Variation in this interaction or its perturbation by genetic and environmental factors could determine the normal spectrum of developmental variation or development of early onset diseases. This study will begin to dissect the principles underlying maternal-zygotic interactions and identify key factors involved.

描述（由申请人提供）：模型有机体果蝇中的初步研究为由于母亲与合子之间的相互作用而引起的发育变化提供了证据，以控制胚胎发生早期事件。该相互作用可能基于对凹槽信号的母体强制的二吻抗性，以限制二拟合子细胞成为生殖细胞的机会。从达尔文人的角度来看，生殖细胞将是默认的命运。 Notch信号的激活将促进发育依赖的替代体细胞命运的采用。母亲和合子似乎使用基于mRNA 3'UTR的机制来调节相互作用。在本R21提案中描述的实验的目的是测试母亲相互作用的证据。通过测试母亲和合子通过MRNA 3'UTR中的序列在早期的胚胎发生事件中动态控制Notch信号的假设来实现此目标。实验是在三个特定目的下设计的：（1）使用果蝇遗传学的能力来测试生殖细胞 - 及其性细胞命运规范中母酶相互作用的预测以及其他三个早期的早期胚胎发生事件； （2）在野生型和遗传操纵的胚胎上使用SNP和分子方法来测试当除去其孕妇或二氏二一个基因时，对Notch途径基因样品的表达谱的变化进行了预测； （3）使用一种分析方法来确定Notch途径基因的样本是否表现出从母亲离子相互作用预测的3'UTR中序列变化的模式。早期的胚胎发生事件比以后的事件更深刻地影响发展，并且在所有发育事件中，Notch途径函数都是相似的。因此，母亲春季相互作用有可能影响广泛的生物学过程，包括细胞命运规范，复杂的发育疾病，干细胞分化的调节以及辅助基于生殖技术的人类妊娠。这项研究可能出现的一条信息是，为了充分了解这些过程，可能有必要适应人群和进化生物学家开发的其他分析工具。 公共卫生相关性：孕产妇和合子基因组第一次见面时的相互作用可以控制早期胎儿发育的许多方面。这种相互作用的变化或对遗传因素和环境因素的扰动的变化可以决定发育变异或早期发作疾病发育的正常光谱。这项研究将开始剖析母体 - 杂种相互作用的原理，并确定所涉及的关键因素。