ROLE OF MORPHOGENETIC PROTEINS IN EMBRYOGENESIS AND TISSUE REGENERATION

形态发生蛋白在胚胎发生和组织再生中的作用

• 批准号: 6101247
• 负责人: M MOOS
• 金额: --
• 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/6101247
• 关键词: adenylate cyclase; bone development; bone regeneration; cartilage development; developmental genetics; developmental neurobiology; embryogenesis; growth factor; nervous system regeneration; neurogenesis; osteogenesis; protein purification; tissue /cell culture; transforming growth factors; vertebrate embryology

Our primary goal is to identify and define the actions of proteins that can be used to repair tissues or structures that have been damaged by trauma, neoplasia, or other pathology. We have identified over a dozen novel proteins. Two of these induce the formation of cartilage, one induces the formation of bone and hematopoietic tissue, one plays a key role in defining the overall pattern of the developing embryo, and thr others have unknown functions. One of these proteins, Frzb, is a secreted inhibitor of signaling by the Wnt growth factor oncogenes, and is the prototype of a growing family of related proteins. Key feedback interactions between secreted growth factors belonging to the Wnt and Bone Morphogenetic Protein (BMP) families and secreted antagonists of these proteins were elucidated. Localized expression of BMPs 4&7, Wnt-8, the BMP antagonists chordin and noggin, and the Wnt antagonist Frzb were found to establish the morphogenetic field giving rise to the earliest precursors of vertebrate muscle. The relationship of expression pattern of these proteins appears to maintain a dynamic balance between Wnt-8 and BMPs 4&7 pathways that controls tissue fate. The dbl oncogene was found to be expressed in a complex pattern within the developing central nervous system, suggesting that this guanine nucleotide exchange protein may have specific functions in neural differentiation. Several novel genes were identified, including a possible homologue of mammalian thymopoietin that begins to be expressed during gastrulation.

我们的主要目标是识别和定义蛋白质的作用 可用于修复已被 创伤、肿瘤或其他病理改变。我们已经确认了十几个 新的蛋白质。其中两种诱导软骨的形成，一种 诱导骨和造血组织的形成，一个起着关键作用 在定义发育中胚胎的总体模式方面的作用，以及 其他的则有未知的功能。其中一种蛋白质，Frzb，是一种分泌的 Wnt生长因子癌基因的信号抑制因子，是 不断增长的相关蛋白质家族的原型。关键反馈 WNT分泌的生长因子与WNT的相互作用 骨形态发生蛋白家族及其分泌型拮抗剂 对这些蛋白质进行了鉴定。骨形态发生蛋白4、7、Wnt-8、 BMP拮抗剂Chordin和Noggin，以及Wnt拮抗剂Frzb 发现建立了最早形成的形态发生场 脊椎动物肌肉的前体。表达模式之间的关系 似乎维持WNT-8和WNT-8之间的动态平衡 控制组织命运的BMPS 4和7通路。发现了Dbl癌基因 在发展中的中心以复杂的模式表达 神经系统，提示这种鸟嘌呤核苷酸交换蛋白 可能在神经分化中具有特定的功能。 几个新的基因被鉴定出来，包括一个可能的同源基因 哺乳动物的胸腺生成素，在原肠形成过程中开始表达。