Semaphorin3f as a Spatial Regulator of Embryogenesis
Date
2019-01-22
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Abstract
During 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.
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Semaphorin, Zebrafish, Vessel, Heart, Retina, Developmental Biology
Citation
Halabi, R. (2019). Semaphorin3f as a Spatial Regulator of Embryogenesis (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.