Localized determinants in vertebrate axis formation

描述（由申请人提供）：人类出生缺陷和癌症通常是由Wnt信号通路的错误调节引起的。在早期脊椎动物胚胎中，体轴的发育非常需要激活胚胎一侧的Wnt通路。在爪蟾（Xenopus）这种主要的轴形成模式生物中，不对称的Wnt信号是通过储存在卵中的母源分子的差异定位实现的。受精后，这些决定因素通过卵皮质的微管旋转运动向未来的背侧转移。对这一过程的干扰导致胚胎缺乏背侧组织。调节皮层旋转不对称和轴形成中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，包括本提案的初步研究，都涉及植物性局部因素。这项研究的长期目标是了解这些局部的作用

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.