REGULATION OF NEURAL CREST DEVELOPMENT BY GROWTH FACTORS

生长因子对神经嵴发育的调节

• 批准号: 2200938
• 负责人: Marthe J Howard
• 金额: $ 8.97万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-03-01 至 1995-11-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2200938
• 关键词: binding proteins; cell cell interaction; cell differentiation; cell migration; chick embryo; collagen; early embryonic stage; embryo /fetus tissue /cell culture; extracellular matrix proteins; gene expression; growth factor; immunocytochemistry; in situ hybridization; integrins; laboratory mouse; laminin; mutant; neural crest; neurogenesis; neurotransmitter receptor; quail; stainings; tissue /cell culture; transforming growth factors

Mechanisms that govern the phenotypic specification and expression of neural crest-derived peripheral neurons are beginning to be elucidated. Rules governing the interaction between progenitor cells and their microenvironment will be important in understanding how the nervous system develops. Neural crest-derived cells constitute the majority of neurons and support cells of the peripheral nervous system but the interactions between these cells and growth factors that regulate the molecular composition of their microenvironment remain poorly understood. The neural crest of mammalian (mouse) and avian (quail or chick) species is a good model system for aspects of human development pertaining to cell-cell interactions and factors governing cell lineage specification and phenotypic expression. Transforming growth factor beta (TGF-beta) is a growth and differentiation factor that shows appropriate spatial and temporal expression to postulate a role in neural crest cell development. TGF-beta affects the expression of extracellular matrix molecules such as laminin and collagen type IV which have been implicated in aganglionosis of the terminal bowel of the lethal spotted (ls/ls) mutant mouse. Use of the ls/ls mouse as a model for aganglionosis (typical of Hirschsprungs disease in humans) will make it possible to ask questions both in-vitro and in-situ about the role of the extracellular matrix in neural crest cell migration and differentiation. Dispersed neural crest cells, organ cultures of tissue previously colonized by neural crest cells and in-situ models, all of which are well suited to the combined biochemical and molecular approaches required for addressing issues of cell migration, differentiation and lineage segregation will be employed. The effects of TGF-beta on expression of extracellular matrix molecules (ECM) by mesenchymal cells located along neural crest cell migration pathways as well as the expression of integrins, a family of cell surface ECM molecule receptors, on neural crest and neural crest derived neurons and glial cells will be studied. The ability of neural crest cells to colonize tissues whose expression of ECM has been altered by TGF-beta will be assessed. Altering ECM expression by TGF-beta, in tissue culture, will make it possible to ask questions on biochemical and molecular levels about the spatial and temporal expression of ECM molecules and evaluate their effect on neural crest cell migration and differentiation. Experiments will seek to distinguish those effects on neural crest-derived cells of TGF-beta that are mediated through the ECM from possible direct action of TGF-beta on the neural crest-derived cells themselves. The experiments will provide new insights into the ways in which neural crest cell migration and differentiation can be modified by growth factors that affect ECM expression.

控制表型规范和表达的机制 神经rest衍生的周围神经元开始阐明。 管理祖细胞及其其相互作用的规则 微环境对于理解神经系统如何很重要 发展。 神经rest衍生的细胞构成大多数神经元 和支持周围神经系统的支持细胞，但相互作用 在这些细胞和调节分子的生长因子之间 其微环境的组成仍然很少了解。 神经 哺乳动物（小鼠）和鸟类（鹌鹑或小鸡）的波峰是一个很好的 与细胞细胞有关的人类发展方面的模型系统 相互作用和有关细胞谱系规范的因素和 表型表达。 转化生长因子β（TGF-beta）是生长和分化 显示适当的空间和时间表达以假定的因素 在神经rest细胞发育中的作用。 tgf-beta影响表达 细胞外基质分子，例如层粘连蛋白和IV型胶原蛋白 这与末端肠的aganglioniso相关 斑点（LS/LS）突变小鼠。 使用LS/LS鼠标作为模型 Aganglioniso（典型的人类Hirschsprungs病的典型）将成为 可能会提出关于视野内和原位的问题 神经rest细胞迁移和分化的细胞外基质。 分散的神经rest细胞，以前定植的组织的器官培养物 通过神经rest细胞和原位模型，所有这些模型都非常适合 解决所需的合并生化和分子方法 细胞迁移，分化和谱系隔离的问题将是 雇用。 TGF-β对细胞外基质表达的影响 分子（ECM）通过位于神经rest细胞的间充质细胞 迁移途径以及整联蛋白的表达，一个细胞家族 表面ECM分子受体，在神经rest和神经rest上 将研究神经元和神经胶细胞。 神经rest细胞的能力 殖民组织的ECM表达已被TGF-β改变了 将被评估。 在组织培养中改变TGF-β的ECM表达， 将有可能就生化和分子水平提出问题 关于ECM分子的空间和时间表达并评估 它们对神经Crest细胞迁移和分化的影响。 实验将寻求区分这些对神经rest衍生的影响 通过可能的直接通过ECM介导的TGF-β细胞 TGF-β对神经rest衍生的细胞本身的作用。 这 实验将为神经冠的方式提供新的见解 细胞迁移和分化可以通过生长因素来改变 影响ECM表达。