PUBLICATION

The development of brain pericytes requires expression of the transcription factor nkx3.1 in intermediate precursors

Authors

Ahuja, S., Adjekukor, C., Li, Q., Kocha, K.M., Rosin, N., Labit, E., Sinha, S., Narang, A., Long, Q., Biernaskie, J., Huang, P., Childs, S.J.

ID

ZDB-PUB-240430-3

Date

2024

Source

PLoS Biology 22: e3002590e3002590 (Journal)

Registered Authors

Childs, Sarah J., Huang, Peng, Kocha, Katrinka

Keywords

none

Datasets

GEO:GSE232762, GEO:GSE232163, GEO:GSE232763

MeSH Terms

Homeodomain Proteins/genetics
Homeodomain Proteins/metabolism
Zebrafish Proteins*/genetics
Zebrafish Proteins*/metabolism
Mesoderm/cytology
Mesoderm/metabolism
Gene Expression Regulation, Developmental
Pericytes*/cytology
Pericytes*/metabolism
Chemokine CXCL12/genetics
Chemokine CXCL12/metabolism
Cell Differentiation*/genetics
Animals
Brain*/embryology
Brain*/metabolism
Transcription Factors*/genetics
Transcription Factors*/metabolism
Signal Transduction
Zebrafish*/embryology
Zebrafish*/genetics
Zebrafish*/metabolism
Receptors, CXCR4/genetics
Receptors, CXCR4/metabolism
Neural Crest/cytology
Neural Crest/metabolism

(all 25)

PubMed

38683849 Full text @ PLoS Biol.

Abstract

Brain pericytes are one of the critical cell types that regulate endothelial barrier function and activity, thus ensuring adequate blood flow to the brain. The genetic pathways guiding undifferentiated cells into mature pericytes are not well understood. We show here that pericyte precursor populations from both neural crest and head mesoderm of zebrafish express the transcription factor nkx3.1 develop into brain pericytes. We identify the gene signature of these precursors and show that an nkx3.1-, foxf2a-, and cxcl12b-expressing pericyte precursor population is present around the basilar artery prior to artery formation and pericyte recruitment. The precursors later spread throughout the brain and differentiate to express canonical pericyte markers. Cxcl12b-Cxcr4 signaling is required for pericyte attachment and differentiation. Further, both nkx3.1 and cxcl12b are necessary and sufficient in regulating pericyte number as loss inhibits and gain increases pericyte number. Through genetic experiments, we have defined a precursor population for brain pericytes and identified genes critical for their differentiation.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
cxcl12b	nkx3-1^ca116/ca116	standard conditions	Prim-15		head	ISH	Fig 4
cxcl12b	WT	standard conditions	Prim-25		head ventral region	ISH	Fig 3
cxcl12b	WT	standard conditions	Prim-15		head	ISH	Fig 4
cxcr4a	WT	standard conditions	Prim-25		head ventral region	ISH	Fig 3
EGFP	c264Tg; ca101Tg; ca41Tg	standard conditions	Protruding-mouth		brain pericyte	IFL	Fig 1
foxf2a	WT	standard conditions	Prim-25		head ventral region	ISH	Fig 3
mCherry	c264Tg; ca101Tg; ca41Tg	standard conditions	Protruding-mouth		brain pericyte	IFL	Fig 1
mCherry	c264Tg; ca101Tg; ca41Tg	standard conditions	Day 4		brain pericyte	IFL	Fig 1
nkx3-1	WT	standard conditions	Prim-15		head posterior region	ISH	Fig 1
nkx3-1	WT	standard conditions	Long-pec	Not Detected	head	ISH	Fig 1

1 - 10 of 18

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	chemical treatment by environment: plerixafor	Protruding-mouth	brain pericyte decreased amount, abnormal	Fig 4
WT	chemical treatment by environment: metronidazole	Long-pec	brain hemorrhagic, abnormal	Fig 2
WT	chemical treatment by environment: metronidazole	Long-pec	brain pericyte decreased amount, abnormal	Fig 2
ca91Tg	standard conditions	Protruding-mouth	brain pericyte increased amount, abnormal	Fig 2
nkx3-1^ca116/ca116	standard conditions	Prim-15	head cxcl12b expression decreased amount, abnormal	Fig 4
nkx3-1^ca116/ca116	standard conditions	Long-pec	brain hemorrhagic, abnormal	Fig 2
nkx3-1^ca116/ca116	standard conditions	Long-pec	central artery decreased diameter, abnormal	Fig 2
nkx3-1^ca116/ca116	standard conditions	Protruding-mouth	brain pericyte decreased amount, abnormal	Fig 2
nkx3-1^ca116/ca116; ca101Tg; ca504Tg	standard conditions	Protruding-mouth	brain pericyte increased amount, abnormal	Fig 5

1 - 9 of 9

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
c264Tg	Tg(UAS-E1B:NTR-mCherry)	Transgenic Insertion
ca41Tg	TgBAC(pdgfrb:EGFP)	Transgenic Insertion
ca42Tg	TgBAC(pdgfrb:GAL4FF)	Transgenic Insertion
ca90Tg	Tg(hsp70l:TagBFP)	Transgenic Insertion
ca91Tg	Tg(hsp70l:TagBFP-2A-nkx3-1)	Transgenic Insertion
ca92Tg	Tg(tbx6:Cre,myl7:GFP)	Transgenic Insertion
ca93Tg	Tg(sox10:Cre,myl7:GFP)	Transgenic Insertion
ca94Tg	Tg(hsp70l:LOXP-STOP-LOXP-H2B-GFP,cryaa:Cerulean)	Transgenic Insertion
ca101Tg	TgBAC(nkx3-1:GAL4-VP16)	Transgenic Insertion
ca116		Small Deletion	nkx3-1

1 - 10 of 13

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
nkx3-1	CRISPR1-nkx3-1	CRISPR

Fish

Fish
c264Tg; ca101Tg
c264Tg; ca101Tg; ca41Tg
c264Tg; ca101Tg; la116Tg
ca91Tg
nkx3-1^ca116/ca116
nkx3-1^ca116/ca116
nkx3-1^ca116/ca116; ca101Tg; ca504Tg
WT

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
Cerulean	EFG	Cerulean
Cre	EFG	Cre
EGFP	EFG	EGFP
GAL4	EFG	GAL4
GAL4FF	EFG	GAL4FF
GFP	EFG	GFP
mCherry	EFG	mCherry
NTR	EFG	NTR
TagBFP	EFG	TagBFP

Mapping

Ahuja et al., 2024 ZDB-PUB-240430-3 PMID:38683849

The development of brain pericytes requires expression of the transcription factor nkx3.1 in intermediate precursors

Ahuja et al., 2024

ZDB-PUB-240430-3
PMID:38683849