Stepwise Coordination of Eye Morphogenesis by Extracellular Matrix

细胞外基质对眼睛形态发生的逐步协调

基本信息

  • 批准号:
    10356085
  • 负责人:
  • 金额:
    $ 36.98万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-03-01 至 2025-02-28
  • 项目状态:
    未结题

项目摘要

Project Summary Developmental defects in eye structure commonly account for visual impairment in newborns. Proper eye structure is initially established via the process of optic cup morphogenesis, during which a series of complex cell and tissue rearrangements transforms the optic vesicle into the optic cup, with neural retina and retinal pigmented epithelium (RPE) enwrapping the newly formed lens. With advances in imaging and computational analysis, work from our lab and others has begun to reveal the cellular events underlying optic cup morphogenesis, however, molecular control of these processes still remains poorly understood. A compelling candidate to play a role in controlling optic cup morphogenesis is the extracellular matrix (ECM), a complex, glycoprotein-rich layer that regulates cell survival, movement, signaling, and polarity. Mutations in certain ECM components can lead to ocular pathologies, such as coloboma, suggesting specific requirements during optic cup morphogenesis. Understanding extrinsic control of morphogenesis also has implications for organoid approaches and strategies. Our previous data indicate that a core molecule, laminin, elicits diverse cellular responses in different eye regions. We also found that separate eye domains are exposed to distinct ECM microenvironments, some of which are assembled via tissue-tissue interactions: specifically, neural crest is required to build basement membrane around the RPE. These data suggest that unique ECM microenvironments may be a crucial driver of regional eye morphogenetic events. Zebrafish provide an ideal model system to study this process: optical transparency and rapid development offer a unique opportunity to directly observe and molecularly dissect eye formation in vivo. We previously developed 4-dimensional imaging and computational techniques to track and visualize cell movements throughout optic cup morphogenesis, and recently, methods for automated quantitative analysis of retinal cell size, shape and orientation. This puts us in a unique position to analyze specific morphogenetic defects arising when particular matrix components are disrupted. In this proposal, we will dissect the region-specific roles of ECM factors, including nidogens, tenascin-C, mmp2, and versican, during eye morphogenesis. We hypothesize that dynamic, region-specific ECM microenvironments elicit unique developmental and morphogenetic responses from distinct eye progenitor domains to drive optic cup morphogenesis. Combining molecular genetics with innovative 4-dimensional live imaging and computational methods, we will test this hypothesis in the following specific aims: (1) determine how ECM microenvironment controls retina morphogenesis and organization; (2) determine how ECM modulatory factors control RPE morphogenesis; and (3) determine functional requirements for tissue contributions to specific ECM microenvironments. The experiments proposed will define the spatiotemporal dynamics of ECM activity and distinct cellular functions executed by region-specific ECM factors during crucial steps of eye formation.
项目总结

项目成果

期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Kristen M Kwan其他文献

Kristen M Kwan的其他文献

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{{ truncateString('Kristen M Kwan', 18)}}的其他基金

IMSD at the University of Utah (IMSD@U2)
犹他大学 IMSD (IMSD@U2)
  • 批准号:
    10550211
  • 财政年份:
    2022
  • 资助金额:
    $ 36.98万
  • 项目类别:
IMSD at the University of Utah (IMSD@U2)
犹他大学 IMSD (IMSD@U2)
  • 批准号:
    10360802
  • 财政年份:
    2022
  • 资助金额:
    $ 36.98万
  • 项目类别:
Stepwise Coordination of Eye Morphogenesis by Extracellular Matrix
细胞外基质对眼睛形态发生的逐步协调
  • 批准号:
    10583547
  • 财政年份:
    2021
  • 资助金额:
    $ 36.98万
  • 项目类别:
Hedgehog Signaling and Cilia in Choroid Fissure Morphogenesis and Coloboma
脉络膜裂形态发生和缺损中的刺猬信号和纤毛
  • 批准号:
    9039608
  • 财政年份:
    2015
  • 资助金额:
    $ 36.98万
  • 项目类别:
Hedgehog Signaling and Cilia in Choroid Fissure Morphogenesis and Coloboma
脉络膜裂形态发生和缺损中的刺猬信号传导和纤毛
  • 批准号:
    9234536
  • 财政年份:
    2015
  • 资助金额:
    $ 36.98万
  • 项目类别:
Hedgehog Signaling in Optic Fissure Morphogenesis and Coloboma
视裂形态发生和缺损中的 Hedgehog 信号传导
  • 批准号:
    10736980
  • 财政年份:
    2015
  • 资助金额:
    $ 36.98万
  • 项目类别:
Stepwise Coordination of Eye Morphogenesis by Extracellular Matrix
细胞外基质对眼睛形态发生的逐步协调
  • 批准号:
    9120882
  • 财政年份:
    2015
  • 资助金额:
    $ 36.98万
  • 项目类别:
Stepwise Coordination of Eye Morphogenesis by Extracellular Matrix
细胞外基质对眼睛形态发生的逐步协调
  • 批准号:
    8945899
  • 财政年份:
    2015
  • 资助金额:
    $ 36.98万
  • 项目类别:
Hedgehog Signaling and Cilia in Choroid Fissure Morphogenesis and Coloboma
脉络膜裂形态发生和缺损中的刺猬信号和纤毛
  • 批准号:
    8864926
  • 财政年份:
    2015
  • 资助金额:
    $ 36.98万
  • 项目类别:
Developmental Biology Training Program
发育生物学培训计划
  • 批准号:
    10627560
  • 财政年份:
    1995
  • 资助金额:
    $ 36.98万
  • 项目类别:

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