Transcription factors in the neural crest gene regulatory network

神经嵴基因调控网络中的转录因子

• 批准号: 1147221
• 负责人: Robert Cornell
• 金额: $ 82.3万
• 依托单位: University of Iowa
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1147221&HistoricalAwards=false
• 关键词: Transcription; factors; neural; crest; gene

The neural crest is a population of migratory stem cells that contributes extensively to development of many of the structures that define vertebrates, including the jaw. Because the neural crest is important both in vertebrate development and in vertebrate evolutionary origins it has been the subject of intense study for decades. It is now well accepted that a cascading network of regulatory molecules collectively known as the neural-crest gene regulatory network commits progenitor cells to the neural-crest fate, and that disruption of this network grossly perturbs development of the animal. It is known that multiple transcription factors and chromatin-modifying proteins, which are two categories of genetic regulatory molecule, contribute to the network. However, the specific interactions among these regulatory molecules remain poorly understood.This question will be tackled using genetic approaches in zebrafish embryos. Embryonic development in zebrafish, as all vertebrates, depends on the neural crest. Zebrafish embryos develop externally of the mother and are transparent. These features make them particularly well suited to investigations of mechanisms of embryonic development shared by all vertebrates.At the conclusion of this work, an understanding of how each of these regulatory molecules fits within the neural crest gene regulatory network will be gained, as well as knowledge of the order of function of each protein and of the nature of the regulatory interactions, i.e. activating or inhibiting, to which they contribute. An understanding of how a transcription factor that is required in multiple cell types is directed to neural-crest specific targets by a chromatin-modifying protein should also be advanced. The potential impact of this work is a profoundly improved understanding of the genetic mechanisms governing neural crest development and vertebrate evolutionary origins. This work will provide training in cutting-edge molecular genetic methods for students from under represented minorities, and includes outreach at local public schools.

神经嵴是一群迁移性干细胞，对脊椎动物包括颌骨在内的许多结构的发育有广泛的贡献。 由于神经嵴在脊椎动物的发育和进化起源中都很重要，因此几十年来一直是深入研究的主题。 现在公认的是，一个级联网络的调节分子统称为神经嵴基因调控网络的承诺祖细胞的神经嵴的命运，这个网络的破坏严重扰乱了动物的发展。已知多种转录因子和染色质修饰蛋白作为两类遗传调控分子参与了该网络。 然而，这些调控分子之间的特定相互作用仍然知之甚少。这个问题将在斑马鱼胚胎中使用遗传方法来解决。 与所有脊椎动物一样，斑马鱼的胚胎发育取决于神经嵴。 斑马鱼胚胎在母体外部发育，是透明的。 这些特征使它们特别适合于研究所有脊椎动物共有的胚胎发育机制。在这项工作的结论中，将获得对这些调控分子中的每一个如何在神经嵴基因调控网络中配合的理解，以及对每种蛋白质的功能顺序和调控相互作用的性质的认识，即激活或抑制，他们所贡献的。 一个转录因子，需要在多种细胞类型的理解是针对神经嵴特异性靶染色质修饰蛋白也应该推进。这项工作的潜在影响是深刻地提高了对神经嵴发育和脊椎动物进化起源的遗传机制的理解。这项工作将为代表性不足的少数群体的学生提供尖端分子遗传学方法的培训，并包括在当地公立学校开展外联活动。