PROTEIN/NUCLEIC ACID INTERACTIONS IN VERTEBRATE EMBRYOGENESIS

脊椎动物胚胎发生中的蛋白质/核酸相互作用

• 批准号: 2575663
• 负责人: THOMAS D sargent
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2575663
• 关键词: Xenopus oocyte; animal genetic material tag; cadherins; cell adhesion molecules; developmental genetics; ectoderm; embryogenesis; genetically modified animals; intermolecular interaction; laboratory mouse; messenger RNA; nucleic acid sequence; protein tyrosine kinase; skin; transcription factor; vertebrate embryology; zebrafish

The general aim of this project is to identify and study the function of factors that regulate vertebrate embryonic development. This is being approached in three ways. One approach is to analyze the regulation and function of Dlx3, one of the vertebrate homologs of the Drosophila gene Distal-less. In flies this gene regulates limb and sensory appendage formation. The frog and mouse homologs are both expressed in epidermis, branchial arches, and in gradients in the limbs. The mouse gene is also active in hair follicles, tooth primordia and other locations. DNA elements and protein-DNA interactions responsible for this expression pattern are being mapped. In addition, targeted inactivation and mis-expression studies are being used to test for the function of Dlx3 gene expression in the epidermis of transgenic mouse embryos. A second approach employed has been to identify mRNAs encoding Eph-related receptor tyrosine kinases that are expressed in specific tissues of early frog embryos. One such kinase, called Pagliaccio, has been shown to affect cell-cell adhesion when constitutively activated in Xenopus embryonic ectoderm, probably by modulating cadherin function. A related gene, TCK, is also being studied. The third approach focuses on the developmental function of calcium-dependent cell adhesion molecules in the zebrafish neural tube. A novel cadherin, VN-cad, has been cloned, sequenced, and characterized by in situ hybridization. Functional studies are being carried out by injection of VN-cad messenger RNA into zebrafish embryos.

本项目的总体目标是确定和研究 调节脊椎动物胚胎发育的因素。这是一种 从三个方面着手。一种方法是分析监管和 果蝇基因的脊椎动物同源物之一DLX3的功能 远端少。在果蝇中，这种基因调节肢体和感觉附属物。 队形。青蛙和小鼠的同源物都在表皮中表达， 鳃弓，以及四肢的渐变。老鼠的基因也是 活跃于毛囊、牙原基等部位。脱氧核糖核酸 导致这种表达的元件和蛋白质-DNA相互作用 模式正在绘制中。此外，有针对性的灭活和 错误表达研究正被用于测试DLX3的功能 转基因小鼠胚胎表皮中的基因表达。 第二种方法是识别编码的mRNAs 特异表达的EPH相关受体酪氨酸激酶 早期青蛙胚胎的组织。其中一种名为Pagliaccio的激酶具有 已被证明在结构性激活时会影响细胞间的黏附 非洲爪哇胚胎外胚层，可能是通过调节钙粘附素的功能。 相关基因TCK也在研究中。 第三种方法侧重于儿童的发育功能 斑马鱼神经管中钙依赖的细胞黏附分子。 一种新的钙粘附素VN-cad已被克隆、测序和鉴定 通过原位杂交。正在进行的功能研究由 将VN-cad信使RNA注入斑马鱼胚胎。