McFarlane, SarahCechmanek, Paula Bernice2018-07-052018-07-052018-06-28Cechmanek, P. B. (2018). Sema6d signaling in the developing visual system (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/32256http://hdl.handle.net/1880/107034The retinal pigment epithelium (RPE) is a highly specialized monolayer of epithelial cells that arise from retinal progenitors and form a tight barrier between the neural retina (eye) and the brain. Although only a thin monolayer, RPE cells perform numerous important functions and are indispensible for mature photoreceptor renewal and survival. When RPE dysfunction occurs, in diseases like Retinitis Pigmentosa and Age-related Macular Degeneration (AMD), devastating vision loss can occur. While much work has focused on understanding RPE function in adult life, little is known about how the RPE arises during early embryonic life or how it spreads to wrap around the neural retina. In this thesis I use zebrafish (Danio rerio) as a model to a) characterize early RPE development, and b) implicate the classical axon guidance cue Semaphorin6d (Sema6d), and its receptor Plexina1 (Plxna1), in RPE and optic cup morphogenesis in the developing zebrafish embryo. I show that markers of RPE differentiation turn on in RPE progenitors prior to optic cup morphogenesis, and that RPE morphogenesis occurs in two phases: First an antero-posterior expansion of the RPE progenitor domain, followed by a second phase coupled to optic cup morphogenesis, where the RPE domain is stretched to form a thin, single-cell epithelium around the eye. Through Sema6d loss-of-function analysis I show that this second phase depends on signals between the Sema6d-expressing progenitors of the temporal neural retina and RPE progenitors expressing Plxna1. This is the first signaling pathway to be identified as a driver for optic cup morphogenesis in any model system. Developing zebrafish as a model system to study early RPE development and retinal cell migration may provide insights to understanding human RPE/retinal cell migration during development and disease.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.SemaphorinPlexinEyeDevelopmental BiologyRetinal Pigment EpitheliumRPESema6DZebrafishMorphogenesisOptic CupTissue Slidingbhlhe40tfecDanio rerioBiologyBiology--CellBiology--Moleculardoctoral thesishttp://dx.doi.org/10.11575/PRISM/32256