Molecular Coordination of Zebrafish Fin Development, Regeneration, and Ray Patterning
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Date
2024-01-10
Authors
Robbins, Amy
Journal Title
Journal ISSN
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Publisher
University of Oregon
Abstract
Danio rerio zebrafish fins and human limbs, although outwardly dissimilar, develop using conserved genetic modules. However, unlike humans, zebrafish can perfectly regenerate their fins following amputation or injury. Therefore, understanding the mechanisms underlying fin development and regeneration may improve our understanding of human limb abnormalities and aid the rational design of therapeutics for injury repair. In this dissertation, I use the branched zebrafish caudal fin skeleton as a model system to explore the fundamental question of how appendages form a precisely patterned skeleton. Our lab previously discovered Sonic hedgehog (Shh) signaling is specifically required for fin ray branching during regeneration. In Chapter II, I extend this understanding to demonstrate Shh mediates ray branching during development of all seven zebrafish fins. Further, I find Shh slows the migration of basal epidermal cells as they pass over immature bone in the distal outgrowing fin. This reinforces a potential heterotypic cell association mechanism by which the Shh+ basal epidermis directs branching during ray formation. In Chapter III, I further detail the development of the caudal fin skeleton. I describe how a subset of fin rays, the peripheral principal rays, differs in ontogeny from other fin rays and propose three organizing centers together produce caudal fin symmetry. Chapter IV uses a zebrafish model of Fraser Syndrome to explore how basement membrane-mediated epithelial-mesenchymal associations contribute to ray branching morphogenesis in development and regeneration. In addition to describing the first adult zebrafish model of Fraser Syndrome, I characterize dramatic fin ray patterning abnormalities including but not limited to unbranched rays. I demonstrate the skeletal patterning abnormalities are Shh signaling-independent, showing the basement membrane (and likely additional extracellular structures) establishes a permissive environment for robust skeletal patterning. Turning back to which signals direct ray branching, I identify wnt10a, which is known to be expressed during fin regeneration, as a putative upstream activator of localized basal epidermal shha. In Chapter V, I generate fin-deficient wnt10a mutants and describe the temporal requirements of Wnt10a for median fin development and regeneration. In Chapter VI, I use the wnt10a mutants to demonstrate Wnt10a activates basal epidermal shha expression and thereby initiates the cooperative cell behaviors underlying ray branching morphogenesis. Collectively, this dissertation advances our understanding of the molecular control of zebrafish fin development, regeneration, and skeletal patterning.
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Keywords
Fin development and regeneration, Ray branching, Shh signlaing, Skeletal patterning, Wnt signlaing, Zebrafish