CELL DIVISION PATTERNING DURING DEVELOPMENT

描述：计划中的实验聚焦于编码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 类被认为与增长因素相关联，并可能作为 共同受体。Dally基因最初在果蝇中被发现是因为 亚形突变导致眼睛中某些有丝分裂的延迟 盘和大脑的板层前体中。与这些单元格关联 周期缺陷是未能抑制G1周期蛋白(A和可能的E)等 他们坚持进入M期。Selleck表明，细胞周期蛋白A的减少 剂量部分地挽救了有丝分裂停止，这表明DAL 表型是这种表达的结果。 在目前的提案中，Selleck希望检验一个特定的假设， 即Dally作为BMP样生长因子DPP的共同受体 而生长因子的局部合成是控制模式的因素 组织的成员。因此，戴利将提供一个独特的句柄 Glypicans在接收生长因子信号。除 抗DALY抗体的制备及生化特性研究 它的细胞表面连接和结构功能，大部分建议 重点研究了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，下游分子 DPP接受的标记(即OMB和SAL基因)是可用的，并且具有 被很好地刻画出来了。其他人则研究同时表达 改变细胞对异位DPP表达的敏感性。塞莱克会的 也继续他对Dal和cell之间关系的描述。 周期调节器，特别是持续存在的机制 细胞周期蛋白E处于中期。DAL间直接物理相互作用的试验 和DPP将使用放射性标记的DPP和之前的 获得抗DAL的抗体，或共电泳法。诱变筛选是 建议在存在的情况下通过筛选获得DAL的真正零等位基因 一种复制，以对抗该基因座潜在的单致死性。

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.