ROLE OF MORPHOGENETIC PROTEINS IN EMBRYOGENESIS AND TISSUE REGENERATION

我们的主要目标是识别和定义蛋白质的作用， 可用于修复被损伤的组织或结构， 创伤、瘤形成或其它病理。我们已经确认了十几个 新型蛋白质其中两种诱导软骨的形成， 诱导骨骼和造血组织的形成，其中一个起着关键作用， 在确定发育胚胎的总体模式中的作用， 其他的功能未知。其中一种蛋白质Frzb是一种分泌型蛋白质， Wnt生长因子癌基因信号传导的抑制剂， 一个不断增长的相关蛋白质家族的原型。关键反馈 属于Wnt的分泌生长因子与 骨形态发生蛋白（BMP）家族和骨形态发生蛋白的分泌拮抗剂 对这些蛋白质进行了鉴定。BMPs 4和7，Wnt-8， BMP拮抗剂chordin和noggin，以及Wnt拮抗剂Frzb， 发现建立了形态发生场， 脊椎动物肌肉的前体。表达模式的关系 这些蛋白质似乎保持Wnt-8和 BMPs 4和7控制组织命运的途径。发现了dbl癌基因 以一种复杂的模式在发展中的中央 神经系统，这表明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，包括一个可能的同源基因， 在原肠胚形成期间开始表达的哺乳动物胸腺生成素。

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.