Variation in maternal and zygotic control of embryogenesis events in Drosophila

描述（由申请人提供）：对模式生物黑腹果蝇的初步研究提供了由于母体和受精卵（后代）之间的相互作用而导致的发育变异的证据，以控制胚胎发生的早期事件。这种相互作用可能是基于合子对母体施加Notch信号以限制合子细胞成为生殖细胞的机会的抵抗。从达尔文的观点来看，生殖细胞将是默认的命运。Notch信号的激活将促进发育所依赖的替代体细胞命运的采用。母体和受精卵似乎使用基于mRNA 3' UTR的机制来调节相互作用。本R21提案中描述的实验目标是测试母体-受精卵相互作用的证据。这一目标将通过验证母体和受精卵通过mrna的3' UTR序列动态控制Notch信号在早期胚胎发生事件中的假设来实现。实验的设计有三个特定目的：(1)利用果蝇遗传学的力量来测试母-受精卵在生殖细胞-体细胞命运规范和其他三个早期胚胎发生事件中的相互作用的预测；(2)利用SNPs和分子方法对野生型和基因操作胚胎进行测试，以预测Notch通路基因样本在母系或合子成分被移除时表达谱的变化；(3)利用分析方法确定Notch通路基因样本是否表现出母代相互作用预测的3' UTR序列变异模式。早期胚胎发生事件对发育的影响比后期更深远，Notch通路在所有发育事件中的功能是相似的。因此，母子相互作用有可能影响广泛的生物过程，包括细胞命运规范、复杂的发育疾病、干细胞分化调节和基于辅助生殖技术的人类妊娠。从这项研究中可能得到的信息是，为了充分理解这些过程，可能有必要采用博弈论分析和其他由人口和进化生物学家开发的分析工具。

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.