CELL DIVISION PATTERNING DURING DEVELOPMENT

描述：拟议的实验集中在dally基因，该基因编码 果蝇中GPI连接的细胞表面蛋白聚糖。 蛋白质在这 类被认为与生长因子有关， 共受体 dally基因最初是在果蝇中发现的， 亚型突变导致眼睛中某些有丝分裂的延迟 盘和大脑的前体层中。 与这些细胞相关 周期缺陷是不能抑制G1周期蛋白（A和可能的E）， 使它们持续到M期。 Selleck表明细胞周期蛋白A的减少 剂量部分挽救有丝分裂停滞，表明dal 表型是这种表达的结果。 在本提案中，Selleck希望测试一个特定的假设， 即Dally作为BMP样生长因子DPP的共受体 生长因子的局部合成控制着 的分裂。 因此，达利将提供一个独特的处理的作用， Glypicans在生长因子信号的接收。 除了有 抗体的生产和生物化学表征 其细胞表面的连接和结构功能，大多数建议 重点是dal和dpp途径之间的相互作用。 其中一些 研究将在翼盘上进行， dpp接收标记（一， 例如，omb和sal基因）可用并且具有 被很好地描述了。 其他人则研究同时表达是否 Dal的表达改变了细胞对异位DPP表达的敏感性。 Selleck将 还继续他的特性之间的关系达尔和细胞 周期调节剂，特别是持久性的机制， 细胞周期蛋白E在中期。 dal之间直接物理相互作用的试验 DPP将使用放射性标记的DPP和先前的 获得Dal抗体或共电泳。 诱变筛选是 建议通过在存在下筛选获得Dal的真无效等位基因， 一个复制以对抗基因座的潜在单倍致死性。

DESCRIPTION: The proposed experiments focus on the dally gene which encodes a GPI linked cell surface proteoglycan in Drosophila. Proteins in this class are thought to associate with growth factors and may function as co-receptors. The dally gene was initially identified in Drosophila because hypomorphic mutations caused a delay in certain mitotic division in the eye disc and in the lamina precursors of the brain. Associated with these cell cycle defects is a failure to repress G1 cyclins (A and possibly E) such that they persist into M phase. Selleck shows that reductions in cyclinA dosage partially rescues the mitotic arrest, suggesting that the dal phenotype is a consequence of this expression. In the present proposal, Selleck wishes to test a specific hypothesis, namely that dally acts as a co-receptor for the BMP like growth factor dpp and that local synthesis of that growth factor is what controls the pattern of division. Dally would therefore provide a unique handle on the role of Glypicans in the reception of growth factor signals. In addition to the production of antibodies to dally and the biochemical characterization of its cell surface linkage and structure function, most of the proposal focuses on the interaction between dal and the dpp pathway. Some of these studies will be carried out on the wing disc where downstream molecular marker for dpp reception (I. e., omb and sal gene) are available and have been well characterized. Others investigate whether simultaneous expression of dal alters a cell's sensitivity to ectopic dpp expression. Selleck will also continue his characterization of the relationship between dal and cell cycle regulators, particularly the mechanisms underlying the persistence of cyclin E in metaphase. Tests for direct physical interactions between dal and dpp will be carried out using radiolabeled dpp and the previously obtained antibodies to dal, or co-electrophoresis. Mutagenesis screens are proposed to obtain true null alleles of dal by screening in the presence of a duplication to counter the potential haplo-lethality of the locus.