Formation of the Drosophila salivary gland

果蝇唾液腺的形成

基本信息

批准号：
8878033
负责人：
Deborah J Andrew
金额：
$ 50.98万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-02-01 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8878033
关键词：
Address Adherens Junction Adhesions Adult Affect Animals Apical Automobile Driving Binding Biogenesis Biological Metamorphosis Cell Death Cell Shape Cell model Cells Coupled Cultured Cells DNA-Binding Proteins Defect Development Drosophila genus Duct (organ) structure Embryo Enzymes Epidermis Epithelial Cells Event Functional disorder Gene Expression Gene Targeting Genes Genetic Gland Goals Head Helix-Turn-Helix Motifs Human In Situ Hybridization Individual Ions Knock-out Lead Learning Legal patent Life Link Lipids Logic Mammary gland Membrane Lipids Metals Modeling Molecular Morphogenesis Movement Mutation Neural Tube Defects Neural tube Organ Organelles Organism Pancreas Physiological Play Prevention Process Production Protein Isoforms Proteins Role Salivary Glands Secretory Cell Secretory Component Spinal Dysraphism Staging System Tissues Tube Tubular formation Winged Helix Work base cell type constriction gene discovery gland development human disease human tissue insight moesin mutant prenatal prevent protein expression tissue culture transcription factor

项目摘要

DESCRIPTION (provided by applicant): The Drosophila salivary gland (SG) is an ideal model for revealing the molecular and cellular events underlying formation and physiological specialization of secretory tubular organs, such as the pancreas, mammary and secretory glands of humans. The SG is a simple tubular organ that forms using the same morphogenetic changes as more complicated organs of higher animals, including changes in cell shape, adhesion and movement. The SG is also the largest secretory organ in the embryo providing an ideal model for how cells achieve high-level secretory capacity and how changes in capacity are coordinated with the expression of secretory content. Three key transcription factors are expressed in the specialized secretory cells of the SG from the onset of gland formation to the early stages of metamorphosis, as well as in the adult SG. Each transcription factor plays major roles in different aspects of SG biogenesis. The winged helix DNA binding protein Fork head (Fkh) is required for SG survival, for morphogenesis and for maintaining expression of itself and other SG-specific transcription factors. The bZip transcription factor CrebA increases secretory capacity by elevating the expression of protein components of secretory organelles and of secreted cargo. The bHLH DNA binding protein Sage is predicted to regulate expression of tissue-specific gene products based on its SG limited expression. Targets of each transcription factor are being discovered by microarray studies and in situ hybridization. These regulators and their targets are an excellent toolset for revealing the details of morphogenesis and the regulatory logic linking morphogenesis to functional specialization. The goals of this proposal are (Aim 1) to characterize the molecular machinery that coordinates apical constriction, a cell shape change required for the formation of many organs; (Aim 2) to identify other key regulators that function with CrebA to achieve high-level secretory capacity in specialized secretory organs; (Aim 3) to identify tissue- specific gene products to learn how their expression is coordinated with morphogenesis and acquisition of secretory capacity. This study is expected to provide new paradigms for how organ morphogenesis and physiological specialization are coupled during development.

描述（由申请人提供）：果蝇唾液腺（SG）是揭示分泌性管状器官（例如胰腺，乳腺和分泌腺体）的分泌性管状器官的分子和细胞事件的理想模型。 SG是一种简单的管状器官，它使用与更复杂的高等动物器官相同的形态发生变化形成，包括细胞形状，粘附和运动的变化。 SG也是胚胎中最大的分泌器官，为细胞如何实现高级分泌能力以及容量变化如何与分泌含量的表达协调的理想模型。从腺体形成开始到变态的早期以及成年SG，在SG的专门分泌细胞中表达了三个关键的转录因子。每个转录因子在SG生物发生的不同方面起主要作用。 SG存活，形态发生以及保持自身和其他SG特异性转录因子的表达是必需的。 BZIP转录因子CREBA通过提升分泌细胞器和分泌货物的蛋白质成分的表达来增加分泌能力。预测BHLH DNA结合蛋白鼠尾草根据其SG有限的表达来调节组织特异性基因产物的表达。通过微阵列研究和原位杂交发现了每个转录因子的靶标。这些调节剂及其目标是揭示形态发生的细节以及将形态发生与功能专业相关的调节逻辑细节的绝佳工具集。该提案的目标是（目标1）表征协调顶端收缩的分子机制，这是许多器官形成所需的细胞形状变化；（目标2）确定其他与CREBA发挥作用的关键调节器，以在专门的分泌器官中实现高级分泌能力；（目标3）鉴定特定于组织的基因产物，以了解其表达如何与形态发生和分泌能力的获取相协调。预计这项研究将为器官形态发生和生理专业化如何在发育过程中提供新的范式。