Lenard, Anna. Dynamic cell rearrangements shape the cranial vascular network of developing Zebrafish embryos. 2013, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_10391
In this study I performed detailed analyses of different fusion events in cranial vessels of the developing zebrafish embryo. Using novel transgenic tools and high resolution live imaging I defined a multistep model of vessel fusion and showed that it is conserved in various vascular beds, regardless of vessel shape and the age of the embryo. I also showed that in all the cranial vessels I studied, the initial fusion steps are the same and involve de novo deposition of junctional proteins, ZO-1 and VE-cadherin, in a form of a junctional spot, which subsequently elaborates into a ring, followed by de novo apical membrane insertion. Lumen formation in the newly formed vessel takes place through blood pressure-dependent luminal/apical cell membrane invagination and fusion of apical membranes, leading to a continuous lumen. During this process, the tip cells become unicellular/seamless tubes with transcellular lumen. I found that such newly connected vessels subsequently undergo dynamic cellular rearrangements that lead to the transformation of the unicellular tubes into multicellular ones. This transformation involves cell splitting, a novel cellular mechanism that, to our knowledge, has not been described before in branching morphogenesis of any organ. Additionally, I analyzed the fusion process in VE-cadherin deficient embryos and showed that this adhesion molecule is necessary for formation of a single contact surface between the fusing vessel sprouts and thus, has an important role in coordinating anastomosis.
I have also analyzed vessel regression during vascular pruning and I showed that it follows a multistep process involving dynamic cell rearrangements that resemble “reversed” vessel fusion. These analyses represent the first studies of vessel remodeling at the cellular level in an in vivo system.
|Committee Members:||Spang, Anne|
|Faculties and Departments:||05 Faculty of Science > Departement Biozentrum > Growth & Development > Cell Biology (Affolter)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||213 S.|
|Last Modified:||30 Jun 2016 10:53|
|Deposited On:||28 Jun 2013 13:57|
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