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Elucidating the role of cell to extracellular matrix adhesion in regulating tissue mechanics during development Goodwin, Katharine Elizabeth
Abstract
Tissue morphogenesis requires force-generating mechanisms to drive the organization of cells into complex three-dimensional structures. Although such mechanisms have been characterized across the metazoan lineage, we know little about how force transmission across a tissue is regulated. Here, using Drosophila melanogaster as a model system, I provide evidence that integrin-mediated cell-ECM adhesion is required for the regulation and transmission of forces in tissues. Specifically I show that during Dorsal Closure (DC), an integrin-dependent morphogenetic process that occurs during Drosophila embryogenesis, failure to regulate the level of cell-ECM adhesion results in abnormal levels of tension in the amnioserosa (AS), an extra-embryonic epithelium that is essential for DC. Integrin-containing adhesive structures were identified on the basal surface of the AS that share many features with focal adhesions. Using mutations that either increase or decrease integrin-based Cell-ECM adhesion, I show that DC is defective in both cases, and that the level of adhesion is inversely correlated with the mobility of cells in the AS. Mathematical modeling, quantitative image analysis, and in vivo laser ablation experiments reveal a relationship between cell mobility and the magnitude, distribution and transmission of tension in the AS. Finally, I provide evidence that mechanical coupling exists between AS cells and their substrate, the underlying ECM and the yolk membrane. Overall, my data shows that integrins regulate the transmission of forces across the AS, and thereby control a critical component of DC. I propose that modulating Cell-ECM adhesion could provide control over force transmission within developing tissues to promote specific outcomes.
Item Metadata
| Title |
Elucidating the role of cell to extracellular matrix adhesion in regulating tissue mechanics during development
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| Creator | |
| Publisher |
University of British Columbia
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| Date Issued |
2015
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| Description |
Tissue morphogenesis requires force-generating mechanisms to drive the organization of cells into complex three-dimensional structures. Although such mechanisms have been characterized across the metazoan lineage, we know little about how force transmission across a tissue is regulated. Here, using Drosophila melanogaster as a model system, I provide evidence that integrin-mediated cell-ECM adhesion is required for the regulation and transmission of forces in tissues. Specifically I show that during Dorsal Closure (DC), an integrin-dependent morphogenetic process that occurs during Drosophila embryogenesis, failure to regulate the level of cell-ECM adhesion results in abnormal levels of tension in the amnioserosa (AS), an extra-embryonic epithelium that is essential for DC. Integrin-containing adhesive structures were identified on the basal surface of the AS that share many features with focal adhesions. Using mutations that either increase or decrease integrin-based Cell-ECM adhesion, I show that DC is defective in both cases, and that the level of adhesion is inversely correlated with the mobility of cells in the AS. Mathematical modeling, quantitative image analysis, and in vivo laser ablation experiments reveal a relationship between cell mobility and the magnitude, distribution and transmission of tension in the AS. Finally, I provide evidence that mechanical coupling exists between AS cells and their substrate, the underlying ECM and the yolk membrane. Overall, my data shows that integrins regulate the transmission of forces across the AS, and thereby control a critical component of DC. I propose that modulating Cell-ECM adhesion could provide control over force transmission within developing tissues to promote specific outcomes.
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| Genre | |
| Type | |
| Language |
eng
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| Date Available |
2016-11-30
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| Provider |
Vancouver : University of British Columbia Library
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| Rights |
Attribution-NonCommercial-NoDerivs 2.5 Canada
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| DOI |
10.14288/1.0216459
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| URI | |
| Degree | |
| Program | |
| Affiliation | |
| Degree Grantor |
University of British Columbia
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| Graduation Date |
2016-02
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| Campus | |
| Scholarly Level |
Graduate
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| Rights URI | |
| Aggregated Source Repository |
DSpace
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Attribution-NonCommercial-NoDerivs 2.5 Canada