FUNCTION OF PRB RELATED PROTEINS IN SKELETAL DEVELOPMENT

描述（改编自申请人的摘要）： 软骨细胞的分化和增殖在 骨骼生成 视网膜母细胞瘤蛋白（pRB）相关的p107和p130 蛋白质与这些过程有关，因为小鼠胚胎 缺乏p107和p130表现出延迟的软骨细胞分化， 骺软骨细胞生长失调。 本研究旨在 建立p107和p130有助于 软骨细胞分化和增殖控制。 这个的目标 主要研究内容有：（1）鉴定胚胎发育的最早期特征 软骨形成需要p107/p130功能，通过确定第一个 间充质细胞凝聚形态、增殖异常 对照和软骨形成相关基因表达， p107/p130缺陷胚胎;（2）鉴定与控制 正常调节依赖于p107/p130功能的软骨形成， 鉴定在野生型中差异表达的基因， 107/p130缺陷胚胎;（3）确定是否诱导 TGF-β样蛋白的软骨形成需要p107/p130功能， 确定这种诱导是否在体外受损， p107/p130缺陷的间充质细胞;（4）确定p107/p130 功能参与早期软骨形成， 细胞周期的退出，通过建立正常的表达模式， p107、p130以及p107和p130的推定调节剂;以及（5）确定 p107和p130如何通过 鉴定在骨骺软骨细胞中失调的基因， p107/p130缺陷胚胎。 这些研究旨在提高我们的 了解细胞生长和分化控制过程， 在软骨内骨发育中具有广泛的重要性。

DESCRIPTION (Adapted from the Applicant's Abstract): The control of chondrocyte differentiation and proliferation plays a central role in skeletogenesis. The retinoblastoma protein (pRB)-related p107 and p130 proteins are implicated in these processes, since mouse embryos that are deficient in p107 and p130 exhibited delayed chondrocyte differentiation and deregulated epiphyseal chondrocyte growth. The study is intended to establish the mechanisms through which p107 and p130 contribute to chondrocyte differentiation and proliferation control. The goals of this study are: (1) to identify the earliest features of embryonic chondrogenesis that require p107/p130 function, by identifying the first abnormalities in mesenchymal cell condensation morphology, proliferation control, and chondrogenesis-associated gene expression that occur in p107/p130-deficient embryos; (2) to identify genes related to the control of chondrogenesis whose normal regulation depends upon p107/p130 function, by identifying genes that are differentially expressed in wild-type and 107/p130-deficient embryos; (3) to establish whether the induction of chondrogenesis by TGF-beta-like proteins requires p107/p130 function, by determining whether such induction is impaired, in vitro, in p107/p130-deficient mesenchymal cells; (4) to determine how p107/p130 function is engaged in early chondrogenesis, and in epiphyseal chondrocyte cell cycle withdrawal, by establishing the normal expression patterns of p107, p130 and putative regulators of p107 and p130; and (5) to determine how p107 and p130 impose control on epiphyseal chondrocyte proliferation, by identifying genes that are deregulated in epiphyseal chondrocytes of p107/p130-deficient embryos. These studies are intended to improve our understanding of cell growth and differentiation control processes that are of wide-ranging importance in endochondral bone development.