Localized determinants in vertebrate axis formation

脊椎动物轴形成的局部决定因素

• 批准号: 8666648
• 负责人: DOUGLAS W HOUSTON
• 金额: $ 29.56万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-11 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8666648
• 关键词: Address; Animal Model; Cell Cycle; Cell Differentiation process; Cell Polarity; Childhood; Congenital Abnormality; Cytoplasm; Data; Development; Diagnosis; Disease; Dorsal; Embryo; Embryonic Development; Feedback; Fertilization; Funding; Future; Gene Activation; Gene Expression; Genes; Genetic Epistasis; Goals; Grant; Hereditary Disease; Human; Human Development; Image; Life; Ligands; Malignant Neoplasms; Measurement; Mediating; Messenger RNA; Methodology; Methods; Microtubule Polymerization; Microtubules; Modeling; Molecular; Molecular Evolution; Monitor; Motion; Movement; Oligonucleotides; Oocytes; Organism; Pathway interactions; Play; Plus End of the Microtubule; Prevention; Process; Proteins; Proteomics; Public Health; Publishing; Rana; Receptor Signaling; Regulation; Relative (related person); Research; Role; Rotation; Side; Signal Pathway; Signal Transduction; Structure; Techniques; Testing; Tissue Differentiation; Tissues; Work; Xenopus; base; cell type; egg; improved; in vivo; insight; loss of function; novel; p23 translationally controlled tumor protein; public health relevance; receptor; research study; success; ubiquitin ligase

DESCRIPTION (provided by applicant): Human birth defects and cancers are often caused by misregulation of the Wnt signaling pathway. In early vertebrate embryos, development of the body axis critically requires the activation of the Wnt pathway on one side of the embryo. In the frog Xenopus, a predominant model organism for axis formation, asymmetric Wnt signaling is achieved by the differential localization of maternally derived molecules stored in the egg. These determinants are translocated toward the future dorsal side by microtubule-based rotational movements of the egg cortex following fertilization. Interference with this process results in embryos lacking the dorsal tissues. The exact mechanisms regulating asymmetry in cortical rotation and Wnt activation in axis formation remain unclear. Data from maternal loss-of- function studies, including preliminary studies for this proposal, have implicated vegetally localized factors. The long-term goal of this research is to understand the role of these localized maternal gene products in embryonic axis formation. Preliminary studies for this proposal have identified a potential for maternal Wnt signals in regulating cortical rotation. Novel methods for monitoring microtubule dynamics during cortical rotation in vivo are also employed. The objectives of this proposal are to determine mechanisms underlying the formation of the vegetal microtubule array and to characterize potential determinants carried on the array. The specific aims are to determine the roles of localized mRNAs in controlling microtubule assembly during the cortical rotation, to determine the extent this process is regulated by ongoing Wnt signaling in the oocyte and to characterize protein determinants in the vegetal cortex.

描述（由申请人提供）：人类出生缺陷和癌症通常由Wnt信号通路的失调引起。在早期脊椎动物胚胎中，体轴的发育关键需要激活胚胎一侧的Wnt通路。在蛙爪蟾中，轴形成的主要模式生物，不对称Wnt信号是通过储存在卵中的母体衍生分子的差异定位实现的。这些决定因素被易位到未来的背侧的微管为基础的旋转运动的卵皮质受精后。干扰这一过程会导致胚胎缺乏背部组织。调节皮质旋转不对称性和轴形成中Wnt激活的确切机制尚不清楚。来自母体功能丧失研究的数据，包括对这一提议的初步研究，都涉及植物性局部因素。这项研究的长期目标是了解这些本地化的 母体基因产物在胚胎轴形成中的作用。这一建议的初步研究已经确定了一个潜在的母亲Wnt信号在调节皮质旋转。还采用了在体内皮质旋转过程中监测微管动力学的新方法。这项建议的目的是确定机制的植物微管阵列的形成和表征潜在的决定因素进行阵列。具体的目的是确定本地化的mRNA在皮质旋转过程中控制微管组装的作用，以确定这一过程是由正在进行的Wnt信号在卵母细胞中的调节程度，并表征植物皮质中的蛋白质决定簇。