PUBLICATION

The SLC7A7 Transporter Identifies Microglial Precursors prior to Entry into the Brain

Authors

Rossi, F., Casano, A.M., Henke, K., Richter, K., Peri, F.

ID

ZDB-PUB-150512-6

Date

2015

Source

Cell Reports 11(7): 1008-17 (Journal)

Registered Authors

Henke, Katrin, Peri, Francesca

Keywords

none

MeSH Terms

Macrophages/cytology*
Macrophages/metabolism
In Situ Hybridization
Embryo, Nonmammalian
Zebrafish Proteins/metabolism*
Amino Acid Transport System y+L/metabolism*
Brain/embryology*
Zebrafish
Microglia/cytology*
Microglia/metabolism
Neurogenesis/physiology
Animals, Genetically Modified
Neural Stem Cells/cytology*
Neural Stem Cells/metabolism
Animals
Cell Differentiation/physiology

(all 16)

PubMed

25959825 Full text @ Cell Rep.

Abstract

During development, macrophages invade organs to establish phenotypically and transcriptionally distinct tissue-resident populations. How they invade and colonize these organs is unclear. In particular, it remains to be established whether they arise from naive equivalents that colonize organs randomly or whether there are committed macrophages that follow pre-determined migration paths. Here, by using a combination of genetics and imaging approaches in the zebrafish embryo, we have addressed how macrophages colonize the brain to become microglia. Identification and cloning of a mutant that lacks microglia has shown that Slc7a7, a Leucine/Arginine transporter, defines a restricted macrophage sub-lineage and is necessary for brain colonization. By taking a photoconversion approach, we show that these macrophages give rise to microglia. This study provides direct experimental evidence for the existence of sub-lineages among embryonic macrophages.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
apoeb	slc7a7^{t30713/t30713}	standard conditions	Day 4	Not Detected	brain	ISH	Fig. 2
apoeb	WT	standard conditions	Day 4		brain microglial cell	ISH	Fig. 2
Kaede	gl24Tg; s1999tTg	standard conditions	26+ somites		anterior lateral plate mesoderm macrophage	IFL	Fig. 1
Kaede	gl24Tg; s1999tTg	standard conditions	Day 4		brain microglial cell	IFL	Fig. 1
Kaede	gl24Tg; s1999tTg	standard conditions	Protruding-mouth		brain microglial cell	IFL	Fig. 1
Kaede	gl24Tg; s1999tTg	standard conditions	Prim-5		macrophage	IFL	Fig. 2
Kaede	gl24Tg; s1999tTg + MO1-slc7a7	standard conditions	Prim-5		macrophage	IFL	Fig. 2
Kaede	hdb2Tg; hdb4Tg	standard conditions	Day 4		brain microglial cell	IFL	Fig. 4
Kaede	hdb2Tg; hdb4Tg	standard conditions	Long-pec		head macrophage	IFL	Fig. 4
Kaede	hdb4Tg	standard conditions	Day 4		brain microglial cell	IFL	Fig. 4

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-slc7a7	standard conditions	Long-pec	brain lacks all parts of type macrophage, abnormal	Fig. 3
WT + MO1-slc7a7	standard conditions	Long-pec	eye lacks all parts of type macrophage, abnormal	Fig. 3
WT + MO1-slc7a7	standard conditions	Day 4	brain lacks all parts of type microglial cell, abnormal	Fig. 3
WT + MO1-slc7a7	standard conditions	Day 4	microglia development decreased occurrence, abnormal	Fig. 3
WT + MO1-spi1b	standard conditions	Day 4	brain lacks all parts of type microglial cell, abnormal	Fig. 3
WT + MO1-spi1b	standard conditions	Day 4	microglia development decreased occurrence, abnormal	Fig. 3
gl24Tg; s1999tTg + MO1-slc7a7	standard conditions	Prim-5	whole organism has normal numbers of parts of type macrophage, normal	Fig. 2
hdb2Tg + MO1-slc7a7	standard conditions	Prim-5	whole organism has normal numbers of parts of type leukocyte, normal	Fig. 2
slc7a7^{t30713/t30713}	standard conditions	Prim-5	whole organism has normal numbers of parts of type leukocyte, normal	Fig. 2
slc7a7^{t30713/t30713}	standard conditions	Prim-5	whole organism has normal numbers of parts of type macrophage, normal	Fig. 2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
gl24Tg	Tg(mpeg1:GAL4-VP16)	Transgenic Insertion
hdb2Tg	Tg(spi1b:GAL4,UAS:TagRFP)	Transgenic Insertion
hdb4Tg	Tg(slc7a7:Kaede)	Transgenic Insertion
i149Tg	Tg(UAS-E1B:NTR-mCherry)	Transgenic Insertion
i186Tg	TgBAC(csf1ra:GAL4-VP16)	Transgenic Insertion
s1999tTg	Tg(UAS-E1B:Kaede)	Transgenic Insertion
t30713		Point Mutation	slc7a7
zf149Tg	Tg(spi1b:GAL4,UAS:EGFP)	Transgenic Insertion

1 - 8 of 8

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Human Disease / Model

Human Disease	Fish	Conditions	Evidence
lysinuric protein intolerance	slc7a7^{t30713/t30713}	standard conditions	TAS
lysinuric protein intolerance	WT + MO1-slc7a7	standard conditions	TAS

Sequence Targeting Reagents

Target	Reagent	Reagent Type
slc7a7	MO1-slc7a7	MRPHLNO
spi1b	MO1-spi1b	MRPHLNO

Fish

Fish
gl24Tg; s1999tTg
gl24Tg; s1999tTg + MO1-slc7a7
hdb2Tg
hdb2Tg; hdb4Tg
hdb2Tg + MO1-slc7a7
hdb4Tg
hdb4Tg; i149Tg; i186Tg
i149Tg; i186Tg
slc7a7^{t30713/t30713}
slc7a7^{t30713/t30713}; gl24Tg; s1999tTg

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Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
GAL4	EFG	GAL4
Kaede	EFG	Kaede
mCherry	EFG	mCherry
NTR	EFG	NTR
TagRFP	EFG	TagRFP

Mapping

Rossi et al., 2015 ZDB-PUB-150512-6 PMID:25959825

The SLC7A7 Transporter Identifies Microglial Precursors prior to Entry into the Brain

Rossi et al., 2015

ZDB-PUB-150512-6
PMID:25959825