Genetic control of animal development

描述(由申请者提供)：我们的总体目标是了解在动物发育过程中对细胞分裂、细胞命运和形态发生进行强有力控制的机制和原理。我们以线虫秀丽线虫为模型，探索基因调控网络如何在不考虑生理和环境条件变化的情况下，产生精确定义的细胞命运的时间和空间模式。线虫是研究在动物发育中对细胞分裂和分化进行强有力控制的遗传和分子机制的理想工具。这是因为线虫细胞谱系发育的时间和空间模式在广泛的生长条件下基本上是不变的，包括温度、养分可获得性和种群密度。为了更好地了解这种显著的应激发育，我们使用了线虫表现出应激敏感表型的发育突变体，并使用这些突变体的遗传和分子分析来识别和表征缓冲线虫发育对抗逆境的遗传调节机制。我们特别讨论了由microRNAs转录后的基因调控如何赋予发育和生理对环境变化的健壮性。这项研究的预期结果包括(来自目标1)更好地理解早期动物胚胎中基因表达程序的强大协调，(来自目标1和2)在温度压力背景下的发育稳定性，以及(来自目标3)在不断变化的环境资源背景下发育速率和细胞命运指定的全球协调。这些结果有望揭示与人类生物学相关的基本原理，包括发育、癌症、组织动态平衡和伤口愈合。

DESCRIPTION (provided by applicant): Our overall goal is to understand the mechanisms and principles underlying the robust control of cell division, cell fate, and morphogenesis during animal development. We employ the nematode worm Caenorhabditis elegans as a model for exploring how genetic regulatory networks produce precisely defined temporal and spatial patterns of cell fates regardless of changing physiological and environmental conditions. C. elegans is ideal for studying the genetic and molecular mechanisms for robust control of cell division and differentiation in animal development. This is because the temporal and spatial patterns of cell lineage development in C. elegans are essentially invariant across a broad range of growth conditions, including temperature, nutrient availability, and population density. To better understand this remarkably stress-robust development, we employ C. elegans developmental mutants that exhibit stress-sensitive phenotypes, and we use genetic and molecular analyses of these mutants to identify and characterize genetic regulatory mechanisms that buffer C. elegans development against stress. We particularly address how post-transcriptional gene regulation by microRNAs confers developmental and physiological robustness against environmental change. The expected outcomes of this study include a better understanding of, (from Aim 1) the robust coordination of gene expression programs in early animal embryos, (from Aims 1 and 2) developmental stability in the context of temperature stresses, and (from Aim 3) the global coordination of developmental rate and cell fate specification in the context of changing environmental resources. These outcomes promise to uncover fundamental principles relevant to human biology, including development, cancer, and tissue homeostasis and wound healing.