Polarity, growth, and morphogenesis of epithelia

上皮细胞的极性、生长和形态发生

基本信息

  • 批准号:
    10312799
  • 负责人:
  • 金额:
    $ 81.97万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-01-01 至 2023-12-31
  • 项目状态:
    已结题

项目摘要

Epithelia are the core cell type of animals, and constitute the most widespread and ancient mode of tissue architecture. Defects in epithelial organization, growth, or morphogenesis underlie a variety of medically devastating disorders, from birth defects to cancer. To understand the biology of humans as well as the rest of the animal kingdom, we need to understand how epithelia take on their distinctive form and how this form enables function. My lab uses a distinctive set of multidisciplinary strategies to investigate these questions in Drosophila, leveraging the deep evolutionary conservation of epithelial biology to uncover general principles applicable across phylogeny. The research described in this MIRA application tackles three fundamental problems of epithelial biology, ranging from the cellular to the tissue and organ scales. First, how are epithelial cells polarized into complementary apical and basolateral domains? Our previous work defined the Scribble module as a basolateral regulator that antagonizes the apical Par complex, but basic questions of the role, relationship, and effector partners of the Scrib proteins remain unanswered, as are the molecular mechanisms that link polarity regulators to the core cellular trafficking machinery. Second, what mechanisms couple growth control in epithelial tissues to cell polarity? We and others have shown that polarity disruption by genetic or physical means activates mitogenic signaling, suggesting that epithelial integrity is an intrinsic control system used to maintain proper size and ensure repair. But how breaches in epithelial homeostasis are detected to trigger proliferation is not understood. Third, how do 3D, multicomponent organs acquire their distinctive shapes? Current paradigms emphasizing cell-autonomous Myosin II contractility derive from analyzing 2D cellular sheets. By studying a simple 3D tube-like organ, we have uncovered multiple novel phenomena including a new morphogenetic movement and an unappreciated mechanism for organ shaping involving extracellular matrix stiffness. Major gaps exist in understanding how cellular and extracellular forces are integrated to drive specific cell behaviors; our expertise uniquely positions us to close these gaps and approach an in toto understanding of organ morphogenesis. The proposed experiments tackle these questions by combining the traditional strengths of Drosophila genetics with new tools with advanced imaging, collaborations with physical scientists, and the development of novel experimental systems. Our results will enhance our understanding of the conserved mechanisms that generate functional epithelial organs during development, and may provide new insights into diseases of epithelial origin.
上皮细胞是动物的核心细胞类型,构成了最广泛和最古老的组织模式

项目成果

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David Bilder其他文献

David Bilder的其他文献

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{{ truncateString('David Bilder', 18)}}的其他基金

Molecular Biology Across Scales Training Program
跨尺度分子生物学培训计划
  • 批准号:
    10555915
  • 财政年份:
    2023
  • 资助金额:
    $ 81.97万
  • 项目类别:
Polarity, growth, and morphogenesis of epithelia
上皮细胞的极性、生长和形态发生
  • 批准号:
    10548124
  • 财政年份:
    2019
  • 资助金额:
    $ 81.97万
  • 项目类别:
Shaping of simple organ by anisotropic biomechanical forces
通过各向异性生物力学力塑造简单器官
  • 批准号:
    8736405
  • 财政年份:
    2014
  • 资助金额:
    $ 81.97万
  • 项目类别:
Shaping of simple organ by anisotropic biomechanical forces
通过各向异性生物力学力塑造简单器官
  • 批准号:
    9329300
  • 财政年份:
    2014
  • 资助金额:
    $ 81.97万
  • 项目类别:
Shaping of simple organ by anisotropic biomechanical forces
通过各向异性生物力学力塑造简单器官
  • 批准号:
    9125853
  • 财政年份:
    2014
  • 资助金额:
    $ 81.97万
  • 项目类别:
PQ6 MECHANISMS OF CACHEXIA LIKE WASTING IN A DROSPHILA CANCER MODEL
果蝇癌症模型中恶病质样消瘦的 PQ6 机制
  • 批准号:
    8591196
  • 财政年份:
    2013
  • 资助金额:
    $ 81.97万
  • 项目类别:
Mechanisms of Drosophila Tumor Suppression
果蝇肿瘤抑制机制
  • 批准号:
    8300880
  • 财政年份:
    2010
  • 资助金额:
    $ 81.97万
  • 项目类别:
Mechanisms of Drosophila Tumor Suppression
果蝇肿瘤抑制机制
  • 批准号:
    8128659
  • 财政年份:
    2010
  • 资助金额:
    $ 81.97万
  • 项目类别:
Mechanisms of Drosophila Tumor Suppression
果蝇肿瘤抑制机制
  • 批准号:
    7991886
  • 财政年份:
    2010
  • 资助金额:
    $ 81.97万
  • 项目类别:
Mechanisms of Drosophila Tumor Suppression
果蝇肿瘤抑制机制
  • 批准号:
    8511701
  • 财政年份:
    2010
  • 资助金额:
    $ 81.97万
  • 项目类别:

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