ROLE OF MORPHOGENETIC PROTEINS IN EMBRYOGENESIS AND TISSUE REGENERATION

在过去的一年里，我们已经确定了与 生长因子的骨形态发生蛋白家族。 这些蛋白质 作为确定职位的关键决定因素 在胚胎发生过程中的信息，并承担了重要性， 生物技术界由于其几乎肯定的治疗效用 在各种临床情况下，包括不愈合骨折和其他 矫形和重建适应症，牙槽嵴增高， 和其他类型的组织修复。 其中之一，抗背化形态发生蛋白（Anti-Dorsalizing Morphogenetic Protein，简称AAPs）， 对整个胚胎的解剖模式产生深远的影响。 虽然 它在胚胎区域表达，与诱导 背部和神经结构，它深刻地抑制他们时， 过度表达AAF是迄今为止唯一确定的此类生长因子。 因为它的表达是在对操纵的反应中增加的， 产生夸张的背部结构，我们建议蛋白质的作用， 作为一个反馈系统， 背侧信号。 这些生长因子不同亚家族的两个成员，最初 在非洲爪蟾基因组DNA中鉴定， 与NIDR的Frank Luyten博士一起，参与了 利用原位杂交和遗传学研究发育脊椎动物肢体 在哺乳动物中。这些基因被称为软骨衍生的形态发生蛋白 （CDMPs）仅在软骨中表达，因此是唯一的生长因子。 已知的特定于这种组织的因素。 我们还分离了哺乳动物成骨蛋白-1（OP-1）的同源物。 该基因表现出复杂和动态的表达模式（腹侧 内胚层/中胚层，眼，耳囊，垂体，松果体，神经轴，和 鳃弓，这表明在胚胎发育过程中的几个不同的角色。 该基因的过表达引起腹侧标记的诱导， 腹部组织明显增生。 BMP家族另一个新成员的部分cDNA克隆已被克隆。 分离自非洲爪蟾。该基因在胚胎的原肠胚形成过程中表达， 胚胎的动物区域;它的生物活性仍然是 鉴定 最后，从牛关节分离的新蛋白质的序列 软骨已被用于分离相应的基因， 在发展过程中展示了一种复杂而动态的表达模式 脊椎动物的肢体 使用简并PCR，我们已经确定了一个同源的 目前正在分离一个完整的cDNA克隆 以研究其在组织修复中的胚胎模式中的作用。

During the past year, we have characterized five genes related to the bone morphogenetic protein family of growth factors. These proteins are emerging as key determinants in the specification of positional information during embryogenesis and have assumed importance to the biotechnology community owing to their almost certain therapeutic utility in a variety of clinical contexts, including nonunion fractures and other orthopedic and reconstructive indications, alveolar ridge augmentation, and other types of tissue repair. One of these , Anti-Dorsalizing Morphogenetic Protein (ADMP), exerts profound effects on the anatomic pattern of the entire embryo. Though it is expressed in the embryonic region associated with induction of dorsal and neural structures, it profoundly suppresses them when overexpressed. ADMP is the only such growth factor identified so far. Because its expression is increased in response to manipulations that produce exaggerated dorsal structures, we propose that the protein acts as a feedback system that moderates the effects of naturally occurring dorsalizing signals in vivo. Two members of a distinct subfamily of these growth factors, originally identified in Xenopus genomic DNA and then characterized in collaboration with Dr. Frank Luyten of NIDR, have been implicated in patterning of the developing vertebrate limb by hybridization in situ and genetic studies in mammals. These genes, termed Cartilage-Derived Morphogenetic Proteins (CDMPs) are expressed only in cartilage, and are thus the only growth factors known that are specific for this tissue. We have also isolated a homolog of mammalian Osteogenic Protein-1 (OP-1). This gene demonstrates a complex and dynamic expression pattern (ventral endoderm/mesoderm, eye, ear vesicle, pituitary, pineal, neural axis, and branchial arches, suggesting several distinct roles during embryogenesis. Overexpression of the gene causes induction of ventral markers and pronounced proliferation of ventral tissue. A partial cDNA clone for another novel member of the BMP family has been isolated from Xenopus. This gene is expressed during gastrulation in the animal region of the embryo; its biological activities remain to be identified. Finally, sequence from a novel protein isolated from bovine articular cartilage has been used to isolate the corresponding gene, which demonstrates a complex and dynamic expression pattern in the developing vertebrate limb. Using degenerate PCR, we have identified a homologous gene in Xenopus and are in the process of isolating a complete cDNA clone to enable study of its role in embryonic patterning in tissue repair.