Drosophila Salivary Gland Morphogenesis

描述(由申请人提供)： 在胚胎发育期间，特定细胞组的形态发生运动被精心安排，以产生具有独特形状和大小的器官。为了了解这种运动发生的机制(S)，我们选择了研究果蝇胚胎唾液腺的早期发育。我们的策略是识别影响唾液腺形态的突变，并通过表征相应的基因，了解细胞形状变化和细胞迁移的细胞和分子基础。从大规模的化学诱变筛选中，我们发现了许多引起唾液腺表型的突变，其中包括一个形成分支唾液腺的毛状新等位基因，以及一组影响唾液腺定向迁移的突变体。我们将确定毛发中的突变如何导致唾液腺分支，而不是形成统一的管，并确定参与细胞形状变化的下游效应器。我们将对唾液腺迁移突变体进行特征分析，并确定其相应的野生型基因。我们将完成对筛选出的剩余突变株的分析，并选择可能存在唾液细胞形状变化缺陷的突变株进行进一步鉴定。这些研究的结果将确定唾液腺形态发生所需的其他基因，并确定它们的作用如何协调，以产生具有独特形状的管状器官。我们从这些研究中获得的理解将广泛应用于其他器官的形成以及某些涉及细胞改变形状和管状形成的疾病，如肿瘤转移。

DESCRIPTION (provided by applicant): During embryonic development, the morphogenetic movements of specified groups of cells are carefully orchestrated to give rise to organs with unique shapes and sizes. To understand the mechanism(s) by which such movements occur, we have chosen to study the early development of the embryonic salivary glands of Drosophila melanogaster. Our strategy is to identify mutations affecting salivary gland morphology, and by characterizing the corresponding genes, learn the cellular and molecular basis of cell shape change and cell migration. From a large-scale chemical mutagenesis screen we identified many mutations that cause interesting salivary gland phenotypes, among which is a new allele of hairy which forms branched salivary glands, and a group of mutants which affect the directed migration of the glands. We will determine how mutations in hairy cause salivary glands to branch instead of form uniform tubes, and identify downstream effectors involved in cell shape change. We will characterize the salivary gland migration mutants and identify their corresponding wild-type genes. We will complete the analysis of the remaining mutant lines from the screen and select mutants with possible defects in salivary cell shape change for further characterization. The results of these studies will identify additional genes required for salivary gland morphogenesis and determine how their roles are coordinated to give rise to a tubular organ with a unique shape. The understanding that we gain from these studies will have wide-reaching applications to the formation of other organs as well to certain diseases where cell change shape and tube formation are involved, such as tumor metastasis.