Krudewig, Alice. Junctional remodeling during angiogenesis : the role of Claudin5 during ISV formation in Zebrafish. 2012, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_9907
To better understand the role of tight junctions during the morphogenetic events of angiogenesis, I have analyzed the function of the endothelial specific Cldn5b during the process of intersegmental vessel (ISV) formation. Although MO-mediated knock-down of cldn5b does not alter the initial outgrowth of endothelial cells (ECs) from the dorsal aorta (DA), it does lead to a halt of EC migration at the level of the horizontal myoseptum (HMS). Furthermore, neighboring ISVs do not connect within the dorsal-longitudinal-anastomotic vessel (DLAV) and detach from the DA. In contrast, the adherens junction specific protein VE-cadherin rather exerts a cell rearrangement function. The different expression pattern of Cldn5b and VE-cadherin support these finding. While VE-cadherin is expressed in every EC of the ISV, Cldn5b is temporally downregulated in early sprouting ECs. Furthermore, a clear reduction of cell number in the ISVs was observed in cldn5b morphants. The latter observation, together with a possible reduction in adhesion between ECs are suggested to cause the phenotypes observed in cldn5b knock-down embryos. Together, this study suggests for the first time a possible role of a Cldn during a morphogenetic event.
Additionally, I generated mutant fish lacking cldn5b gene function by using Zinc-Finger Nucleases. The analysis of these mutant fish will help to understand the functional role of a core component of tight junctions during vertebrate blood vessel development. However, the preliminary analysis show only a very weak ISV phenotype compared to cldn5b morphants. I will discuss several ideas explaining the discrepancy between cldn5b morphants and mutants.
|Committee Members:||Zeller, Rolf|
|Faculties and Departments:||05 Faculty of Science > Departement Biozentrum > Growth & Development > Cell Biology (Affolter)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||182 Bl.|
|Last Modified:||30 Jun 2016 10:49|
|Deposited On:||06 Jul 2012 09:16|
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