Reciprocal Signaling In Skeletogenesis

形成骨骼的细胞首先形成特定的形状，然后分化形成坚硬的， 支撑结构元素。腭裂是最常见的出生缺陷之一， 在骨骼形成的模式阶段，以及骨关节炎，这将影响近五分之一的美国人， 在未来的十年中，源于骨骼组织分化和组织发生的控制受到干扰。 这两种疾病都可能与发育调节基因的功能不正常有关， 控制骨骼发育的细胞之间的相互信号传递。我们的项目早期调查 斑马鱼的发育阶段，以了解骨骼发生中的相互信号。我们假设 形成腭骨骨架的一条途径涉及音速刺猬，血小板， 衍生生长因子和其它信号。我们假设控制软骨组织发生的途径 软骨替代骨涉及骨形态发生蛋白之间的特定相互作用，印度 hedgehog和甲状旁腺激素相关蛋白。为了验证这些假设，我们将详细研究 异常的发育和骨骼表型，这些表型是由这些基因的功能紊乱引起的。 途径。我们还建议进行正向和反向基因筛选，以确定新的骨骼肌。 变种人我们的研究结果将提高我们对颅上皮细胞和 间充质，软骨和骨祖细胞之间，从而告知我们的理解， 腭裂和骨关节炎的发病机制。

Cells that form the skeleton first become patterned into specific shapes, and then differentiate to form stiff, supporting, structural elements. Cleft palate, one of the most common birth defects, arises from disruptions in the patterning phase of skeletogenesis, and osteoarthritis, which will affect nearly one in five Americans during the coming decade, stem from disturbed control of skeletal tissue differentiation and histogenesis. Both disorders can appear with improper functioning of developmental regulatory genes that control reciprocal signaling between cells that govern skeletal development. Our project investigates early developmental stages of zebrafish to understand reciprocal signaling in skeletogenesis. We hypothesize that a pathway patterning the palatal skeleton involves specific interactions among Sonic hedgehog, Platelet- derived growth factor, and other signals. We hypothesize that a pathway controlling histogenesis of cartilage and cartilage-replacement bone involves specific interactions among Bone morphogenetic proteins, Indian hedgehog, and Parathyroid hormone related protein. To test these hypotheses, we will examine the detailed abnormal developmental and skeletal phenotypes that arise by perturbing functions of genes in these pathways. We also propose to carry out forward and reverse genetic screens to identify new skeletal mutants. Our findings will improve our knowledge of signaling pathways between cranial epithelia and mesenchyme, and between cartilage and bone progenitors, and thereby inform our understanding of the pathogenesis of cleft palate and osteoarthritis.