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Elworthy, Stone; Savage, Aaron M.; Wilkinson, Robert N.; Malicki, Jarema J.; Chico, Timothy J.A.
Developmental dynamics, June 2019, 2019-06-00, 20190601, Letnik: 248, Številka: 6Journal Article
Abstrct Background Cilia are essential for morphogenesis and maintenance of many tissues. Loss‐of‐function of cilia in early Zebrafish development causes a range of vascular defects, including cerebral hemorrhage and reduced arterial vascular mural cell coverage. In contrast, loss of endothelial cilia in mice has little effect on vascular development. We therefore used a conditional rescue approach to induce endothelial cilia ablation after early embryonic development and examined the effect on vascular development and mural cell development in postembryonic, juvenile, and adult Zebrafish. Results ift54(elipsa)‐mutant Zebrafish are unable to form cilia. We rescued cilia formation and ameliorated the phenotype of ift54 mutants using a novel Tg(ubi:loxP‐ift54‐loxP‐myr‐mcherry,myl7:EGFP)sh488 transgene expressing wild‐type ift54 flanked by recombinase sites, then used a Tg(kdrl:cre)s898 transgene to induce endothelial‐specific inactivation of ift54 at postembryonic ages. Fish without endothelial ift54 function could survive to adulthood and exhibited no vascular defects. Endothelial inactivation of ift54 did not affect development of tagln‐positive vascular mural cells around either the aorta or the caudal fin vessels, or formation of vessels after tail fin resection in adult animals. Conclusions Endothelial cilia are not essential for development and remodeling of the vasculature in juvenile and adult Zebrafish when inactivated after embryogenesis. Key Findings We successfully rescued homozygous ift54 mutants using a rescue trangene expressing wild type ift54, which partially recovered cilia formation and function. Endothelial specific inactivation of ift54 (required for cilia formation) did not affect endothelial patterning in juvenile and adult zebrafish. Endothelial ift54 inactivation had no effect on mural cell coverage in juveniles and adult zebrafish.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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