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Characterization of Endothelial Cilia Distribution During Cerebral-Vascular Development in Zebrafish ( Danio rerio). Arterioscler Thromb Vasc Biol 2018 12;38(12):2806-2818

Date

12/21/2018

Pubmed ID

30571172

Pubmed Central ID

PMC6309420

DOI

10.1161/ATVBAHA.118.311231

Scopus ID

2-s2.0-85058925854   12 Citations

Abstract

Objective- Endothelial cells (ECs) sense and respond to flow-induced mechanical stress, in part, via microtubule-based projections called primary cilia. However, many critical steps during vascular morphogenesis occur independent of flow. The involvement of cilia in regulating these stages of cranial vascular morphogenesis is poorly understood because cilia have not been visualized in primary head vessels. The objective of this study was to investigate involvement of cilia in regulating the early stages of cranial vascular morphogenesis. Approach and Results- Using high-resolution imaging of the Tg(kdrl:mCherry-CAAX) y171 ;(bactin::Arl13b:GFP) zebrafish line, we showed that cilia are enriched in the earliest formed cranial vessels that assemble via vasculogenesis and in angiogenic hindbrain capillaries. Cilia were more prevalent around the boundaries of putative intravascular spaces in primary and angiogenic vessels. Loss of cardiac contractility and blood flow, because of knockdown of cardiac troponin T type 2a ( tnnt2a) expression, did not affect the distribution of cilia in primary head vasculature. In later stages of development, cilia were detected in retinal vasculature, areas of high curvature, vessel bifurcation points, and during vessel anastomosis. Loss of genes crucial for cilia biogenesis ( ift172 and ift81) induced intracerebral hemorrhages in an EC-autonomous manner. Exposure to high shear stress induced premature cilia disassembly in brain ECs and was associated with intracerebral hemorrhages. Conclusions- Our study suggests a functional role for cilia in brain ECs, which is associated with the emergence and remodeling of the primary cranial vasculature. This cilia function is flow-independent, and cilia in ECs are required for cerebral-vascular stability.

Author List

Eisa-Beygi S, Benslimane FM, El-Rass S, Prabhudesai S, Abdelrasoul MKA, Simpson PM, Yalcin HC, Burrows PE, Ramchandran R

Authors

Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin
Pippa M. Simpson PhD Chief, Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Animals, Genetically Modified
Cerebral Arteries
Cerebral Veins
Cilia
Endothelial Cells
Endothelium, Vascular
Gene Expression Regulation, Developmental
Green Fluorescent Proteins
Intracranial Arteriovenous Malformations
Luminescent Proteins
Mechanotransduction, Cellular
Morphogenesis
Neovascularization, Physiologic
Troponin T
Zebrafish
Zebrafish Proteins
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d