Variation in maternal and zygotic control of embryogenesis events in Drosophila

描述（由申请方提供）：在模式生物黑腹果蝇中的初步研究提供了由于母体和受精卵（后代）之间的相互作用导致的发育变异的证据，以控制胚胎发生中的早期事件。这种相互作用可能是基于合子对Notch信号传导的母体实施的抗性，以限制合子细胞成为生殖细胞的机会。从达尔文的角度来看，生殖细胞将是默认的命运。Notch信号传导的激活将促进发育所依赖的替代体细胞命运的采用。母亲和受精卵似乎使用基于mRNA 3' UTR的机制来调节相互作用。在R21建议中描述的实验的目的是测试母亲-合子相互作用的证据。这一目标将通过检验母体和受精卵通过mRNA的3' UTR中的序列动态控制早期胚胎发生事件中的Notch信号传导的假设来实现。实验设计有三个具体目标：（1）利用果蝇遗传学的力量来检验在生殖细胞-体细胞命运特化和其他三个早期胚胎发生事件中来自母-合子相互作用的预测;（二）在野生型和遗传操作的胚胎上使用SNP和分子方法来测试Notch途径基因样品的表达谱变化的预测，当它们的母体或合子组件被移除;和（3）使用分析方法来确定Notch途径基因的样品是否表现出由母体-子代相互作用预测的3' UTR中的序列变异模式。早期胚胎发生事件可以比后期事件更深刻地影响发育，并且Notch途径功能在所有发育事件中是相似的。因此，母子相互作用有可能影响广泛的生物学过程，包括细胞命运特化、复杂的发育疾病、干细胞分化的调节和基于辅助生殖技术的人类妊娠。这项研究可能会出现的一个信息是，为了充分理解这些过程，可能有必要适应博弈论分析和人口和进化生物学家开发的其他分析工具。 公共卫生相关性：当母体和合子基因组第一次相遇时，它们之间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遗传和环境因素对其的干扰可以决定发育变异的正常范围或早发性疾病的发展。这项研究将开始剖析母合子相互作用的基本原则，并确定涉及的关键因素。

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.