Semaphorin3f as a Spatial Regulator of Embryogenesis

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dc.contributor.advisorMcFarlane, Sarah
dc.contributor.authorHalabi, Rami
dc.contributor.committeememberChilds, Sarah J.
dc.contributor.committeememberHuang, Peng
dc.date2019-06
dc.date.accessioned2019-01-24T17:01:37Z
dc.date.available2019-01-24T17:01:37Z
dc.date.issued2019-01-22
dc.description.abstractDuring embryogenesis, cells integrate both spatial and temporal information from their surroundings to influence proliferation, migration, differentiation and physiological functions. Understanding the molecular mechanisms which confer spatial identity is essential to our understanding of tissue development and human disease. In this thesis I explore multiple roles for the secreted chemotactic ligand Semaphorin3f (Sema3f) in different biological contexts. Using zebrafish (Danio rerio) as a model I take advantage of the duplicated genome to study loss of function of both orthologs, Sema3fa and Sema3fb, in discrete contexts due to their differential expression. First, I show that in the eye Sema3fa produced by progenitors is necessary for the generation of amacrine cells within the temporal retina and the spatially-organized transcriptome of stem cells in the ciliary marginal zone (CMZ). Second, I define an endogenous role of Sema3fa to maintain the avascularity of the neural retina and refine the branch pattern of intraocular vessels. Loss of Sema3fa results in the pathologic angiogenesis of leaky blood vessels into the neural retina. Last, I unveil a role for Sema3fb produced by cardiomyocyte progenitors in the differentiation of the ventricle of the developing heart. Overall, my work provides the first evidence of a Sema3 involved in retinal progenitor cell and cardiomyocyte differentiation, and elucidates the endogenous role of Sema3fa as a negative regulator of retinal blood vessels in the embryo and adult. My data exemplifies the necessity of spatial information conferred by a single chemotactic molecule, Sema3f, to impact differentiation and cellular biology.en_US
dc.identifier.citationHalabi, R. (2019). Semaphorin3f as a Spatial Regulator of Embryogenesis (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/35766
dc.identifier.urihttp://hdl.handle.net/1880/109507
dc.language.isoenen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen
dc.rightsUniversity 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.en_US
dc.subjectSemaphorinen_US
dc.subjectZebrafishen_US
dc.subjectVesselen_US
dc.subjectHearten_US
dc.subjectRetinaen_US
dc.subjectDevelopmental Biologyen_US
dc.subject.classificationBiology--Cellen_US
dc.subject.classificationGeneticsen_US
dc.subject.classificationBiology--Molecularen_US
dc.subject.classificationNeuroscienceen_US
dc.subject.classificationPhysiologyen_US
dc.titleSemaphorin3f as a Spatial Regulator of Embryogenesisen_US
dc.typedoctoral thesisen_US
thesis.degree.disciplineMedicine – Neuroscienceen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameDoctor of Philosophy (PhD)en_US
ucalgary.item.requestcopytrue
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