Variation in maternal and zygotic control of embryogenesis events in Drosophila

描述(申请人提供)：对模式生物黑腹果蝇的初步研究提供了母亲和受精卵(后代)之间相互作用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强制执行Notch信号的抵抗，以限制合子细胞成为生殖细胞的机会。从达尔文的观点来看，生殖细胞将是默认的命运。Notch信号的激活将促进采用发育所依赖的交替体细胞命运。母亲和受精卵似乎使用基于mRNA3‘非编码区的机制来调节相互作用。R21提案中描述的实验的目标是测试母亲-受精卵相互作用的证据。这一目标将通过检验这一假设来实现，即母亲和受精卵通过mRNAs的3‘UTR区序列动态地控制早期胚胎发生过程中的Notch信号。实验是在三个特定目标下设计的：(1)使用果蝇遗传学的力量来测试生殖细胞-体细胞命运规范和其他三个早期胚胎发生事件中母亲-受精卵相互作用的预测；(2)使用SNPs和分子方法对野生型和基因操纵的胚胎进行测试，以测试当移除其母体或受精卵成分时Notch途径基因样本的表达谱变化的预测；以及(3)使用分析方法来确定Notch途径基因样本是否表现出从母子相互作用预测的3‘UTR中的序列变化模式。早期胚胎发育事件比后期事件对发育的影响更深远，而且Notch通路在所有发育事件中的功能都是相似的。因此，母子相互作用有可能影响广泛的生物学过程，包括细胞命运指定、复杂的发育疾病、干细胞分化的调节以及基于辅助生殖技术的人类怀孕。这项研究可能产生的一个信息是，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种群和进化生物学家开发的分析工具。 公共卫生相关性：母体和合子基因组的产物第一次见面时的相互作用可能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的扰动可能决定发育变异或早期疾病发展的正常谱。这项研究将开始剖析母体-受精卵相互作用的基本原理，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.