Determining the molecular underpinnings of extracellular matrix breakdown during choroid fissure closure

dc.contributor.advisorGross, Jeffrey Martin
dc.contributor.committeeMemberWallingford, John B
dc.creatorWilliams, Andre Matthew
dc.creator.orcid0000-0003-1710-4108 2016
dc.description.abstractProper closure of the choroid fissure (CF), a transient structure present during early eye development, is critical for eye organogenesis. Choroid fissure closure (CFC) is a dynamic process that requires morphogenetic movements, extracellular matrix (ECM) breakdown, and tissue fusion. Defects in this process result in coloboma, which is responsible for 3-11% of childhood blindness worldwide. Little is known about the mechanism of ECM breakdown during CFC, or what tissues are responsible for facilitating it. We hypothesized that podosomes, small actin-based structures that are capable of breaking down ECM in other cellular contexts, are responsible for ECM breakdown during CFC. Using a mutant of the actin-linker protein Talin, we show that Talin is not responsible for ECM breakdown, as normal ECM breakdown occurs in talin [superscript HI3093Tg] mutants. Mutation of tks4, a core podosome component, results in a small coloboma, suggesting a likely role for podosomes in proper retinal fusion. Previous data suggested that the hyaloid vasculature, which passes through the CF to envelop the lens, is involved in degrading the ECM during CFC. Though the hyaloid vasculature is present, Actin within the hyaloid vasculature did not localize to regions that have intact ECM, suggesting that the hyaloid vasculature is not involved in ECM breakdown. Finally, I used chicken as a potential new model organism to investigate mechanisms of breakdown in CFC. However, no ECM breakdown was observed in chicken CFC, and invasion of mesenchymal cells that separates the CF was observed. Further investigation is required to determine the molecular underpinnings of CFC.
dc.description.departmentCellular and Molecular Biology
dc.subjectChoroid fissure
dc.subjectEye development
dc.subjectPeriocular mesenchyme
dc.titleDetermining the molecular underpinnings of extracellular matrix breakdown during choroid fissure closure
dc.type.materialtext and Molecular Biology and Molecular Biology University of Texas at Austin of Arts

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