Semaphorin3f in the maturation of the outer retina
Date
2020-09-25
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Abstract
Cells of multicellular organisms have the remarkable ability to coordinate and control dynamic cellular activities in response to changes in their environment. From development into tissue homeostasis, cells communicate with each other through a myriad of intercellular signalling mechanisms. The large family of Semaphorins is a group of well-known extracellular signalling molecules implicated in a wide range of diverse physiological functions. In particular, the expression of secreted Class III Semaphorins (Sema3s) in the retina, not only during development but also in adult tissue, raises interesting questions about their tissue-specific spatiotemporal roles. The vertebrate retina is a highly complex, light-sensitive tissue that lines the back of our eyes. Within the retina, there are two key players that enables our ability to see: the retinal pigment epithelium (RPE) and the photoreceptors. Located in the outermost layer of the retina, the RPE and photoreceptors develop and mature together throughout the lifetime of the organism, forming an interdependent relationship that is highly critical for visual function. This thesis explores, using CRISPR/Cas9-generated loss-of-function mutants (sema3faca304), cell autonomous and non-cell autonomous roles of an RPE-secreted protein, Semaphorin3f (Sema3f), in the zebrafish retina. First, I demonstrate that both cell types, the RPE and photoreceptors, express multiple members of well-known Sema3 receptors, Nrp and PlxnA families. Second, I define a cell autonomous role of Sema3fa in maturing RPE. The loss of Sema3fa does not affect the maturation of the RPE at the transcriptional and morphological level, but does result in the perturbation of appropriate physiological responses to light conditions. Last, I demonstrate the non-cell autonomous role of Sema3fa in the development and specification of maturing photoreceptors. My work elucidates one of the many endogenous roles of Sema3fa as a regulator of the maturing retina to add to the growing literature of Sema signalling in events other than development.
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Semaphorin, RPE, photoreceptors, zebrafish, retina
Citation
Mori-Kreiner, R. (2020). Semaphorin3f in the maturation of the outer retina (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.