PUBLICATION

Fatty Acid Binding Protein 11a Is Required for Brain Vessel Integrity in Zebrafish

Authors: Zhang, J., Qi, J., Wu, S., Peng, L., Shi, Y., Yang, J., Yin, Z., Gao, Y., Wang, C., Gong, J., Zhang, H., Zhang, J., Liu, D.
ID: ZDB-PUB-170427-6
Date: 2017
Source: Frontiers in Physiology 8: 214 (Journal)
Registered Authors: Gao, Yu, Gong, Jie, Qi, Jialing, Shi, Yunwei, Yang, Jinxian, Yin, Zhenhua, Zhang, Jingjing
Keywords: FABP4, fabp11a, knockout, vessel permeability, zebrafish
MeSH Terms: none
PubMed: 28443032 Full text @ Front. Physiol.

Abstract

The monolayer of endothelial cells (ECs) lining the intima of all blood vessel wall forms a semipermeable barrier that regulates tissue-fluid homeostasis, transport of nutrients, and migration of blood cells across the barrier. A number of signaling pathways and molecules mediate endothelial permeability, which plays important roles in a variety of the physiological and pathological conditions. Fatty acid binding proteins (FABPs) are able to bind various hydrophobic molecules, such as long-chain fatty acids, prostaglandins and eicosanoids. FABP4, a member of the family of FABPs, plays an important role in maintenance of glucose and lipid homeostasis as well as angiogenesis. In the present study, we found that fabp11a, the ortholog of mammalian FABP4, was highly expressed in developing brain vessels of zebrafish. Knockout of fabp11a gene caused hemorrhage in zebrafish brain. Morpholino mediated fabp11a gene knockdown phenocopied the hemorrhage in mutants. Furthermore, we demonstrated permeability of brain vessels in fabp11a mutant is significantly higher than that of control. In addition, COX and LOX inhibition partially rescued the brain vessel integrity defects caused by fabp11a loss-of-function, suggesting the integrity defect was relevant to the Fatty Acid function.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
DsRed	sd2Tg	control	Long-pec	blood	IFL	Fig. 3
DsRed	sd2Tg + CRISPR1-fabp4a	standard conditions	Long-pec	blood	IFL	Fig. 3
EGFP	s843Tg	control	Protruding-mouth	brain vasculature	IFL	Fig. S1
EGFP	s843Tg	control	Protruding-mouth	brain vasculature	IFL	Fig. 4
EGFP	s843Tg	control	Long-pec	brain vasculature	IFL	Fig. 3
EGFP	s843Tg	control	Protruding-mouth	brain vasculature	IFL	Fig. S2
EGFP	s843Tg	chemical treatment by environment: SB 203580	Protruding-mouth	brain vasculature	IFL	Fig. S2
EGFP	s843Tg	chemical treatment by environment: N(gamma)-nitro-L-arginine methyl ester	Protruding-mouth	brain vasculature	IFL	Fig. S2
EGFP	s843Tg	chemical treatment by environment: sirolimus	Protruding-mouth	brain vasculature	IFL	Fig. S2
EGFP	s843Tg + CRISPR1-fabp4a	standard conditions	Protruding-mouth	brain vasculature	IFL	Fig. 4

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB + CRISPR1-fabp4a	standard conditions	Long-pec	brain blood mislocalised, abnormal	Fig. 3
AB + CRISPR1-fabp4a	standard conditions	Long-pec	brain hemorrhagic, abnormal	Fig. 3
AB + CRISPR1-fabp4a	standard conditions	Protruding-mouth	brain hemorrhagic, abnormal	Fig. 5
AB + CRISPR1-fabp4a	chemical treatment by environment: indometacin	Protruding-mouth	brain hemorrhagic, ameliorated	Fig. 5
AB + CRISPR1-fabp4a	chemical treatment by environment: lornoxicam	Protruding-mouth	brain hemorrhagic, ameliorated	Fig. 5
AB + CRISPR1-fabp4a	chemical treatment by environment: nordihydroguaiaretic acid	Protruding-mouth	brain hemorrhagic, ameliorated	Fig. 5
AB + MO2-fabp4a	standard conditions	Protruding-mouth	brain blood mislocalised, abnormal	Fig. S1
AB + MO2-fabp4a	standard conditions	Protruding-mouth	brain hemorrhagic, abnormal	Fig. S1
s843Tg	chemical treatment by environment: N(gamma)-nitro-L-arginine methyl ester	Protruding-mouth	blood vasculature decreased branchiness, abnormal	Fig. S2
s843Tg	chemical treatment by environment: N(gamma)-nitro-L-arginine methyl ester	Protruding-mouth	blood vasculature morphology, abnormal	Fig. S2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
s843Tg	Tg(kdrl:EGFP)	Transgenic Insertion
sd2Tg	Tg(gata1a:DsRed)	Transgenic Insertion

Human Disease / Model

Sequence Targeting Reagents

Fish

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
DsRed	EFG	DsRed
EGFP	EFG	EGFP

Mapping

Zhang et al., 2017 ZDB-PUB-170427-6 PMID:28443032

Fatty Acid Binding Protein 11a Is Required for Brain Vessel Integrity in Zebrafish

Zhang et al., 2017

ZDB-PUB-170427-6
PMID:28443032