Genetic Analysis of Epithelial Morphogenesis and Organ Shape
上皮形态发生和器官形状的遗传分析
基本信息
- 批准号:7948098
- 负责人:
- 金额:$ 28.58万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-07-01 至 2015-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdhesionsAnteriorBasement membraneBiochemicalBiologicalCell PolarityCell physiologyCellsComplementCongenital AbnormalityDevelopmentDrosophila genomeDrosophila genusEmbryonic DevelopmentEmployee StrikesEpithelialEpitheliumEventExtracellular MatrixEyeFilamentFilopodiaGeneticGenetic ScreeningGenetic TechniquesGoalsHeartImage AnalysisImaging TechniquesIndividualInvestigationKidneyLabyrinthLifeMediatingMetabolic DiseasesMicrofilamentsMolecularMorphogenesisMutationNeural tubeNursesOocytesOrganPathway interactionsPatternPhosphotransferasesPlayPopulationProcessPublishingRegulation of Cell ShapeResearchRestRoleScreening procedureShapesSideSignal PathwaySignal TransductionSurfaceSystemTestingTissuesWingWorkanterior chambercell behaviorcell typedesigneggflygene functiongenetic analysisgenetic manipulationinterestmigrationmutantnovelpolarized cellpublic health relevance
项目摘要
DESCRIPTION (provided by applicant): The long term goal of this research is to determine how the dynamic regulation of cell shape, polarity and adhesion across cell populations sculpts an organ's shape during development. To this end, we are using genetic and cell biological approaches in Drosophila to investigate how a novel form of planar polarity within the follicle cell epithelium creates the elongated shape of a simple organ-like unit known as an egg chamber. Planar polarity is a developmental mechanism in which individual cells are coordinately polarized within the plane of a tissue to provide directional information for subsequent morphogenetic events. Pioneering work on this phenomenon in the fly wing and eye led to the discovery of the Frizzled planar cell polarity pathway, which is now known to shape the vertebrate body axis, inner ear, kidneys and neural tube. The Frizzled signaling cassette plays no role in egg chamber elongation, however, indicating that the investigation of this process is likely to define a new and perhaps similarly conserved molecular framework regulating planar polarity and organ shape. Our first two specific aims are designed to elucidate the cellular mechanisms that underlie this unconventional planar polarity system. Aim 1 will use genetic manipulations to test the hypothesis that a specialized cell type known as the polar cells induces planar polarity in the neighboring follicle cells, while Aim 2 will use fixed and live imaging techniques to explore the development and function of a polarized cell protrusive activity that represents the most dramatic morphological readout of planar polarity in this tissue. To complement these cellular analyses, we performed a pilot genetic screen that identified a key molecular pathway regulating planar patterning and morphogenesis in this epithelium. Aim 3 will use genetic and biochemical approaches to investigate the function of this signaling cascade, and Aim 4 will employ a highly efficient screening strategy to extend the search for novel egg shape regulators to other regions of the Drosophila genome. Together these studies will reveal the cellular and molecular mechanisms controlling follicle cell planar polarity and egg chamber elongation, and are likely to reveal general principles guiding organ morphogenesis in wide range of systems.
PUBLIC HEALTH RELEVANCE: The proper function of vital organs requires that they attain their proper shapes during embryonic development. When these processes go awry, birth defects metabolic diseases result. The goal of this research is to use the experimental tractability of fruit flies to reveal novel cellular and molecular mechanisms guiding organ morphogenesis.
描述(由申请人提供):本研究的长期目标是确定细胞群体中细胞形状、极性和粘附的动态调节如何在发育过程中塑造器官的形状。为此,我们在果蝇中使用遗传和细胞生物学方法来研究卵泡细胞上皮内一种新的平面极性形式是如何形成一个细长形状的简单器官样单位(称为卵室)的。平面极性是一种发育机制,其中单个细胞在组织平面内协调极化,为随后的形态发生事件提供方向信息。对这种现象在苍蝇翅膀和眼睛上的开创性工作导致了卷曲平面细胞极性通路的发现,现在已知它塑造了脊椎动物的体轴、内耳、肾脏和神经管。然而,卷曲的信号盒在卵室伸长中没有作用,这表明对这一过程的研究可能定义了一种新的、可能类似保守的分子框架,可以调节平面极性和器官形状。我们的前两个具体目标旨在阐明这种非常规平面极性系统的细胞机制。Aim 1将使用遗传操作来验证一种被称为极性细胞的特殊细胞类型在邻近的卵泡细胞中诱导平面极性的假设,而Aim 2将使用固定和实时成像技术来探索极化细胞突出活动的发展和功能,该活动代表了该组织中最引人注目的平面极性形态学解读。为了补充这些细胞分析,我们进行了一个试点遗传筛选,确定了调节上皮平面模式和形态发生的关键分子途径。Aim 3将使用遗传和生化方法来研究这一信号级联的功能,Aim 4将采用一种高效的筛选策略,将寻找新的卵形调节因子扩展到果蝇基因组的其他区域。总之,这些研究将揭示控制卵泡细胞平面极性和卵室伸长的细胞和分子机制,并有可能揭示在广泛的系统中指导器官形态发生的一般原理。
项目成果
期刊论文数量(0)
专著数量(0)
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Sally Horne-Badovinac其他文献
Sally Horne-Badovinac的其他文献
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{{ truncateString('Sally Horne-Badovinac', 18)}}的其他基金
Mechanisms of epithelial migration and basement membrane assembly
上皮迁移和基底膜组装的机制
- 批准号:
10552458 - 财政年份:2023
- 资助金额:
$ 28.58万 - 项目类别:
Mechanisms of basement membrane secretion and assembly
基底膜分泌和组装机制
- 批准号:
10352423 - 财政年份:2020
- 资助金额:
$ 28.58万 - 项目类别:
Genetic Analysis of Epithelial Morphogenesis and Organ Shape
上皮形态发生和器官形状的遗传分析
- 批准号:
8495358 - 财政年份:2010
- 资助金额:
$ 28.58万 - 项目类别:
Genetic Analysis of Epithelial Morphogenesis and Organ Shape
上皮形态发生和器官形状的遗传分析
- 批准号:
8102065 - 财政年份:2010
- 资助金额:
$ 28.58万 - 项目类别:
Genetic Analysis of Epithelial Morphogenesis and Organ Shape
上皮形态发生和器官形状的遗传分析
- 批准号:
8286939 - 财政年份:2010
- 资助金额:
$ 28.58万 - 项目类别:
Genetic Analysis of Epithelial Morphogenesis and Organ Shape
上皮形态发生和器官形状的遗传分析
- 批准号:
8691894 - 财政年份:2010
- 资助金额:
$ 28.58万 - 项目类别:
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