Sema6d Signaling in the Developing Visual System

Cechmanek, Paula Bernice

Sema6d Signaling in the Developing Visual System

dc.contributor.advisor	McFarlane, Sarah
dc.contributor.author	Cechmanek, Paula Bernice
dc.contributor.committeemember	Grewal, Savraj S.
dc.contributor.committeemember	Schuurmans, Carol
dc.date	2018-11
dc.date.accessioned	2018-07-05T14:23:04Z
dc.date.available	2018-07-05T14:23:04Z
dc.date.issued	2018-06-28
dc.description.abstract	The 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.	en_US
dc.identifier.citation	Cechmanek, 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/32256	en_US
dc.identifier.doi	http://dx.doi.org/10.11575/PRISM/32256
dc.identifier.uri	http://hdl.handle.net/1880/107034
dc.language.iso	eng
dc.publisher.faculty	Cumming School of Medicine
dc.publisher.faculty	Graduate Studies
dc.publisher.institution	University of Calgary	en
dc.publisher.place	Calgary	en
dc.rights	University 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.
dc.subject	Semaphorin
dc.subject	Plexin
dc.subject	Eye
dc.subject	Developmental Biology
dc.subject	Retinal Pigment Epithelium
dc.subject	RPE
dc.subject	Sema6D
dc.subject	Zebrafish
dc.subject	Morphogenesis
dc.subject	Optic Cup
dc.subject	Tissue Sliding
dc.subject	bhlhe40
dc.subject	tfec
dc.subject	Danio rerio
dc.subject.classification	Biology	en_US
dc.subject.classification	Biology--Cell	en_US
dc.subject.classification	Biology--Molecular	en_US
dc.title	Sema6d Signaling in the Developing Visual System
dc.type	doctoral thesis
thesis.degree.discipline	Neuroscience
thesis.degree.grantor	University of Calgary
thesis.degree.name	Doctor of Philosophy (PhD)
ucalgary.item.requestcopy	true