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: 6108042
• 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/6108042
• 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

This program is aimed at answering two basic questions in developmental biology. (1) How do differentiating cells regulate changing patterns of gene expression during development? (2) How do migrating cells, such as neural crest cells, find their correct paths in the embryo? To address the first question we use the differentiation of murine epidermal cells as a model system, with a focus on the function and regulation of Dlx3, a homeodomain gene transcribed in upper strata of the epidermis. We have shown by gain-of-function experiments that Dlx3 can regulate, possibly directly, the expression of structural genes activated late in the differentiation process. Loss-of-function (gene ablation) studies have revealed that Dlx3 is essential for survival of the mouse embryo beyond 11 days of gestation. A critical function in formation or function of the placenta is hypothesized based on expression data. Studies in yeast and HeLa cells have shown that Dlx3 acts as a positive regulator of transcription. Cooperating factors and target genes are currently being sought by interaction screens and subtractive hybridization methods. The problem of regulating cell migration is being addressed by analyzing the function of a receptor tyrosine kinase, EphA4 (previously Pagliaccio or SEK1). EphA4 is expressed in involuting mesoderm, in a subset of migrating cranial neural crest, and other tissues undergoing migration or rearrangement. It has been shown to play a critical role in the formation of boundaries between segments in the vertebrate hindbrain. We have shown that when this receptor is activated in early Xenopus embryos there is a significant but transient reduction in cell-cell adhesion, probably by modulation of cadherin function. Recent data indicate that this effect on adhesion is mediated at least in part by the src-related tyrosine kinase c-fyn. Further studies on this signaling pathway, and its role in development, are underway.

本节目旨在回答发展中的两个基本问题 生物学。(1)分化细胞如何调控细胞分化模式的变化 在发育过程中的基因表达？(2)迁移细胞，如 神经脊细胞，在胚胎中找到它们正确的路径？ 为了回答第一个问题，我们用小鼠的分化 以表皮细胞为模型系统，重点研究其功能和功能。 同源结构域基因DLX3的调控 表皮。我们已经通过函数增益实验表明，DLX3可以 可能直接调节被激活的结构基因的表达 在分化过程的后期。功能丧失(基因消融) 研究表明，DLX3对小鼠的生存是必不可少的 妊娠超过11天的胚胎。信息或信息的关键功能 胎盘的功能是基于表情数据来假设的。 在酵母和HeLa细胞中的研究表明，DLX3作为一种阳性 转录调节因子。协同因子和靶基因是 目前正在被交互屏幕和减法搜索 杂交法。 调控细胞迁移的问题正在通过分析 受体酪氨酸激酶EphA4(以前称为Pagliaccio)的功能 或SEK1)。EphA4在退化的中胚层中表达，在 移行的颅神经脊和其他经历移行或 重新编排。它已被证明在 脊椎动物后脑各节段之间边界的形成。我们 已经表明，当这种受体在非洲爪哇早期胚胎中被激活时 细胞间黏附显著但短暂地减少， 可能是通过钙粘附素功能的调节。最近的数据表明， 这种对黏附的影响至少部分是由src相关的 酪氨酸激酶c-fyn。对这一信号通路的进一步研究，以及 它在发展中的作用正在进行中。