Primary cilia are present on endothelial cells of the hyaloid vasculature but are not required for the development of the blood-retinal barrier.
Adaptor Proteins, Signal Transducing
/ genetics
Animals
Animals, Genetically Modified
Blood-Retinal Barrier
/ drug effects
Cilia
/ metabolism
Endothelial Cells
/ cytology
Hedgehog Proteins
/ antagonists & inhibitors
Larva
/ metabolism
Mutagenesis
Retinal Vessels
/ cytology
Signal Transduction
Veratrum Alkaloids
/ pharmacology
Zebrafish
/ growth & development
Zebrafish Proteins
/ genetics
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
31
10
2019
accepted:
14
07
2020
entrez:
1
8
2020
pubmed:
1
8
2020
medline:
5
9
2020
Statut:
epublish
Résumé
Endothelial cilia are found in a variety of tissues including the cranial vasculature of zebrafish embryos. Recently, endothelial cells in the developing mouse retina were reported to also possess primary cilia that are potentially involved in vascular remodeling. Fish carrying mutations in intraflagellar transport (ift) genes have disrupted cilia and have been reported to have an increased rate of spontaneous intracranial hemorrhage (ICH), potentially due to disruption of the sonic hedgehog (shh) signaling pathway. However, it remains unknown whether the endothelial cells forming the retinal microvasculature in zebrafish also possess cilia, and whether endothelial cilia are necessary for development and maintenance of the blood-retinal barrier (BRB). In the present study, we found that the endothelial cells lining the zebrafish hyaloid vasculature possess primary cilia during development. To determine whether endothelial cilia are necessary for BRB integrity, ift57, ift88, and ift172 mutants, which lack cilia, were crossed with the double-transgenic zebrafish strain Tg(l-fabp:DBP-EGFP;flk1:mCherry). This strain expresses a vitamin D-binding protein (DBP) fused to enhanced green fluorescent protein (EGFP) as a tracer in the blood plasma, while the endothelial cells forming the vasculature are tagged by mCherry. The Ift mutant fish develop a functional BRB, indicating that endothelial cilia are not necessary for early BRB integrity. Additionally, although treatment of zebrafish larvae with Shh inhibitor cyclopamine results in BRB breakdown, the Ift mutant fish were not sensitized to cyclopamine-induced BRB breakdown.
Identifiants
pubmed: 32735563
doi: 10.1371/journal.pone.0225351
pii: PONE-D-19-30359
pmc: PMC7394433
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Hedgehog Proteins
0
IFT57 protein, zebrafish
0
Veratrum Alkaloids
0
Zebrafish Proteins
0
cyclopamine
ZH658AJ192
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0225351Subventions
Organisme : NEI NIH HHS
ID : P30 EY025585
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY026181
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY027083
Pays : United States
Organisme : NEI NIH HHS
ID : T32 EY024236
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
J Cell Sci. 2008 Jun 1;121(11):1907-15
pubmed: 18492793
Development. 2004 Aug;131(16):4085-93
pubmed: 15269167
Development. 1996 Dec;123:263-73
pubmed: 9007246
BMC Dev Biol. 2007 Oct 15;7:114
pubmed: 17937808
Exp Eye Res. 2017 Nov;164:82-89
pubmed: 28743502
J Cell Sci. 2010 Feb 15;123(Pt 4):499-503
pubmed: 20144997
Cilia. 2015 Sep 30;4:11
pubmed: 26430510
Dev Cell. 2007 May;12(5):767-78
pubmed: 17488627
Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5519-23
pubmed: 8516294
Cell Rep. 2014 Mar 13;6(5):799-808
pubmed: 24561257
J Pharm Sci. 2011 Sep;100(9):3904-11
pubmed: 21638281
Dev Dyn. 2009 Jul;238(7):1744-59
pubmed: 19517571
Nat Rev Mol Cell Biol. 2002 Nov;3(11):813-25
pubmed: 12415299
Development. 2005 Dec;132(23):5199-209
pubmed: 16251212
Br J Pharmacol. 2016 Jan;173(1):15-26
pubmed: 26276677
Nat Cell Biol. 2010 Apr;12(4):407-12
pubmed: 20305649
Vision Res. 2009 Feb;49(4):479-89
pubmed: 19136023
J Cell Biol. 2018 May 7;217(5):1651-1665
pubmed: 29500191
FASEB J. 2018 Oct;32(10):5674-5684
pubmed: 29874129
J Am Soc Nephrol. 2010 Aug;21(8):1326-33
pubmed: 20576807
Genes Dev. 2008 Mar 15;22(6):734-9
pubmed: 18347092
Stroke. 2007 Dec;38(12):3289-91
pubmed: 17962594
Neuron. 2004 Jun 10;42(5):703-16
pubmed: 15182712
Curr Hypertens Rev. 2016;12(1):57-67
pubmed: 26122329
Adv Exp Med Biol. 2012;763:70-84
pubmed: 23397619
Exp Eye Res. 2014 Dec;129:107-18
pubmed: 25447564
Neurobiol Dis. 2008 Nov;32(2):200-19
pubmed: 18790057
Mech Dev. 2010 Apr;127(3-4):159-68
pubmed: 20156556
BMC Dev Biol. 2010 Jul 23;10:76
pubmed: 20653957
EMBO Rep. 2016 Feb;17(2):156-66
pubmed: 26769565
J Am Soc Nephrol. 2015 Apr;26(4):864-75
pubmed: 25214579
Arterioscler Thromb Vasc Biol. 2018 Dec;38(12):2806-2818
pubmed: 30571172
Acta Neurochir Suppl. 2008;105:73-7
pubmed: 19066086
Differentiation. 2012 Feb;83(2):S56-61
pubmed: 22169885
J Comp Neurol. 1994 Feb 22;340(4):566-76
pubmed: 8006217