Analysis of Noelin, a Neural Crest Competence Factor

神经嵴能力因子 Noelin 的分析

• 批准号: 6718405
• 负责人: Marianne Bronner
• 金额: $ 33.52万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-15 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6718405
• 关键词: biological signal transduction; biomarker; cell migration; confocal scanning microscopy; electroporation; embryo /fetus; embryogenesis; gene mutation; gene targeting; genetically modified animals; glycoproteins; green fluorescent proteins; immunoprecipitation; laboratory mouse; neural crest; neural information processing; neural plasticity; neural plate /tube; protein binding; protein structure function; yeast two hybrid system

DESCRIPTION (provided by the applicant): The vertebrate neural crest appears to form via an inductive interaction between the non-neural ectoderm and the neural plate, thus requiring both a source of inducer (the ectoderm) and a competent receiving tissue (the neural plate). Molecules expressed in the early neural plate may be involved in rendering the tissue "competent" to respond to neural crest induction. By screening neural crest/tube libraries, we have identified a secreted factor, Noelin-1, which is expressed in the prospective avian neural plate and may play a role in making the neural tube competent to form neural crest. Noelin-1 mRNA predicts a protein with a signal peptide, N-glycosylation sites and an olfactomedin-related domain; it is secreted when over-expressed in frog oocytes. Noelin-1 mRNA is expressed in a graded pattern in the closing neural tube, with highest expression in the neural folds and no detectable expression at the ventral midline. The proposed experiments will extend the preliminary findings to further characterize the role of Noelin-1 in early embryonic development. Our working premise is that Noelin-1 bestows competence onto neural tube cells to form neural crest. Noelin is expressed in the intermediate neural plate at a time that correlates with the neural plate's ability to respond to induction by the non-neural ectoderm. Recent work from our laboratory suggests that Wnts may be the initial neural crest inducers and that BMPs may function later to maintain/expand newly-induced neural crest population. Thus, Noelin promises to be a particularly exciting factor since little is known about biological properties underlying tissue competence and how competence factors interact with inducers. We hypothesize that: (1) Noelin-1 renders the neural plate competent to respond to an inductive signal from the surface ectoderm by functioning as a co-receptor; (2) maintenance of neural crest markers in the dorsal neural tube may involve a combination of Noelin plus BMP or other neural tube signals; and (3) Noelin expression is repressed by ventral neural tube signals like Sonic hedgehog. We will test these hypotheses by isolating Noelin binding partners, determining its functional requirements and analyzing the tissue/cellular interactions that mediate its expression. The goal of this proposal is to further characterize the function of Noelin-1 at the molecular and cellular level. Specific experiments will: (1) Determine the nature of molecules that interact with Noelin-1. (2) Determine the function of Noelin in imparting competence to neural tube cells to generate neural crest. (3) Generate and characterize the phenotype of Noelin-1 null mutant. (4) Examine the environmental regulation of Noelin-1 expression.

描述（由申请人提供）：脊椎动物神经嵴似乎 通过非神经外胚层和神经外胚层之间的诱导相互作用形成 神经板，因此需要诱导物来源（外胚层）和 有能力的接受组织（神经板）。早期表达的分子 神经板可能参与使组织“有能力”响应 神经嵴诱导通过筛选神经嵴/管文库，我们获得了 确定了一种分泌因子，Noelin-1，它在预期的 鸟类的神经板，并可能发挥作用，使神经管主管， 形成神经嵴Noelin-1 mRNA预测具有信号肽的蛋白质， N-糖基化位点和嗅觉调节素相关结构域;当 在青蛙卵母细胞中过度表达。Noelin-1 mRNA以分级模式表达 在闭合神经管中，在神经褶中表达最高，而在神经管中没有表达。 在腹侧中线处可检测到表达。拟议的实验将 扩展初步研究结果，以进一步表征Noelin-1在 早期胚胎发育。我们的工作前提是Noelin-1赋予 在神经管细胞上形成神经嵴。Noelin表达于 中间神经板在与神经板的 对非神经外胚层诱导的反应能力。最近的工作从 我们的实验室表明，Wnt可能是最初的神经嵴诱导剂， BMPs可能在以后起作用以维持/扩展新诱导的神经嵴 人口因此，诺埃林有望成为一个特别令人兴奋的因素，因为 对组织能力的生物学特性知之甚少， 能力因素如何与诱导因素相互作用。 我们假设：（1）Noelin-1使神经板有能力响应 从表面外胚层的感应信号， 辅助受体;（2）维持背神经管中的神经嵴标记 可能涉及Noelin加BMP或其他神经管信号的组合;以及 (3)Noelin的表达被腹侧神经管信号如Sonic抑制 刺猬。我们将通过分离Noelin结合配偶体来测试这些假设， 确定其功能需求并分析组织/细胞 相互作用，介导其表达。本提案的目的是 进一步从分子水平和细胞水平研究Noelin-1的功能， 水平具体实验将：（1）确定分子的性质， 与Noelin-1相互作用。(2)确定Noelin在传授中的作用 神经管细胞产生神经嵴的能力。(3)生成并 表征Noelin-1无效突变体的表型。(4)检查 Noelin-1表达的环境调节。