CELL DIVISION PATTERNING DURING DEVELOPMENT

发育过程中的细胞分裂模式

• 批准号: 2685118
• 负责人: SCOTT B SELLECK
• 金额: $ 20.56万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2685118
• 关键词: Drosophilidae; cell cycle; cyclins; developmental genetics; gene expression; growth factor receptors; protein structure function; proteoglycan; radiotracer; site directed mutagenesis

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.

描述：拟议的实验重点关注编码的 dally 基因 果蝇中 GPI 连接的细胞表面蛋白多糖。 这里面的蛋白质 类被认为与生长因子相关，并且可能起到 共受体。 dally 基因最初是在果蝇中发现的，因为 亚等位性突变导致眼睛某些有丝分裂的延迟 椎间盘和大脑的前体层中。 与这些细胞有关 周期缺陷是指未能抑制 G1 细胞周期蛋白（A 和可能的 E），例如 他们持续进入M期。 Selleck 表明 cyclinA 的减少 剂量部分挽救了有丝分裂停滞，表明 dal 表型是该表达的结果。 在目前的提案中，Selleck 希望测试一个特定的假设， 即 dally 充当生长因子 dpp 等 BMP 的共同受体 生长因子的局部合成是控制模式的因素 的划分。 因此，戴利将为角色提供独特的处理方式。 磷脂酰肌醇蛋白聚糖参与生长因子信号的接收。 除了 Dally 抗体的产生及其生化特征 其细胞表面连接和结构功能，大部分提案 重点研究 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，其中下游分子 dpp 接收标记（即 omb 和 sal 基因）可用并且具有 得到了很好的表征。 其他人研究是否同时表达 dal 改变细胞对异位 dpp 表达的敏感性。 塞莱克将 还继续描述了 dal 和细胞之间的关系 循环调节剂，特别是持久性的机制 细胞周期蛋白 E 处于中期。 测试 dal 之间的直接物理相互作用 并且 dpp 将使用放射性标记的 dpp 和之前的 获得 dal 抗体，或共电泳。 诱变筛选是 建议通过在存在的情况下筛选来获得 dal 的真正无效等位基因 复制以对抗基因座潜在的单倍致死性。