PUBLICATION

Trim33 / Tif1-γ is essential for macrophage and neutrophil mobilisation to developmental or inflammatory cues

Authors

Demy, D.L., Tauzin, M., Lancino, M., le Cabec, V., Redd, M., Murayama, E., Maridonneau-Parini, I., Trede, N., Herbomel, P.

ID

ZDB-PUB-170721-7

Date

2017

Source

Journal of Cell Science 130(17): 2797-2807 (Journal)

Registered Authors

Demy, Doris-Lou, Herbomel, Philippe, Lancino, Mylène, Murayama, Emi, Redd, Michael, Tauzin, Muriel, Trede, Nick

Keywords

Amoeboid motility, In vivo, Leukocyte recruitment, Macrophages, Neutrophils, Tif1-gamma, Trim33, Zebrafish

MeSH Terms

Bacterial Infections/pathology
Neutrophils/metabolism*
Mice
Myeloid Cells/metabolism
Cell Movement
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism
Transcription Factors/deficiency
Transcription Factors/genetics
Transcription Factors/metabolism*
Animals
Retina/pathology
Bone Marrow Cells/metabolism
Microglia/metabolism
Central Nervous System/metabolism
Central Nervous System/pathology
Inflammation/metabolism
Inflammation/pathology*
Macrophages/metabolism*
Mutation/genetics

(all 20)

PubMed

28724755 Full text @ J. Cell Sci.

Abstract

Macrophages infiltrate and establish in developing organs from an early stage, often before these have become vascularized. Similarly, leukocytes, in general, can quickly migrate through tissues to any site of wounding. This unique capacity is rooted in their characteristic amoeboid motility, the genetic basis of which is poorly understood. Trim33 (also known as Tif1-γ), a nuclear protein that associates with specific DNA-binding transcription factors to modulate gene expression, has been found to be mainly involved in hematopoiesis and gene regulation mediated by TGF-β. Here, we have discovered that in Trim33-deficient zebrafish embryos, primitive macrophages are unable to colonize the central nervous system to become microglia. Moreover, both macrophages and neutrophils of Trim33-deficient embryos display a reduced basal mobility within interstitial tissues, and a profound lack of a response to inflammatory recruitment signals, including local bacterial infections. Correlatively, Trim33-deficient mouse bone marrow-derived macrophages display a strongly reduced three-dimensional amoeboid mobility in fibrous collagen gels. The transcriptional regulator Trim33 is thus revealed as being essential for the navigation of macrophages and neutrophils towards developmental or inflammatory cues within vertebrate tissues.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
csf1ra	trim33^{t30813/t30813} (TU)	control	Protruding-mouth	midbrain macrophage	ISH	Fig. 2
csf1ra	trim33^{t30813/t30813} (TU)	control	Long-pec	retina macrophage	ISH	Fig. 2
csf1ra	trim33^{tb222b/tb222b} (TU)	control	Prim-25	macrophage	ISH	Fig. S2
csf1ra	TU	control	Prim-25	macrophage	ISH	Fig. S2
csf1ra	TU	control	Protruding-mouth	midbrain macrophage	ISH	Fig. 2
csf1ra	TU	control	Long-pec	retina macrophage	ISH	Fig. 2
EGFP	trim33^{t30813/t30813}; zdf11Tg	control	Prim-15	retina macrophage	IFL	Fig. 3
EGFP	zdf11Tg	control	Prim-15	retina macrophage	IFL	Fig. 3
GFP	i114Tg; ump2Tg	control	Long-pec	neutrophil	IFL	Fig. 4
GFP	i114Tg; ump2Tg	resection: caudal fin	Protruding-mouth	neutrophil	IFL	Fig. 5

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
TU + MO4-trim33	control	Protruding-mouth	optic tectum lacks parts or has fewer parts of type microglial cell, abnormal	Fig. 1
f12Tg; f13Tg + MO4-trim33	control	Prim-5	whole organism apoptotic process increased occurrence, abnormal	Fig. S1
f12Tg; f13Tg; sd2Tg + MO4-trim33	control	Prim-5	erythroid progenitor cell apoptotic, abnormal	Fig. S1
trim33^{t30813/t30813} (TU)	control	14-19 somites	blood island apoptotic process increased occurrence, abnormal	Fig. S1
trim33^{t30813/t30813} (TU)	control	14-19 somites	blood island lacks all parts of type erythroid progenitor cell, abnormal	Fig. S1
trim33^{t30813/t30813} (TU)	control	Long-pec	central nervous system macrophage decreased amount, abnormal	Fig. 2
trim33^{t30813/t30813} (TU)	control	Long-pec	head macrophage decreased amount, abnormal	Fig. 2
trim33^{t30813/t30813} (TU)	control	Long-pec	macrophage migration decreased process quality, abnormal	Fig. 2
trim33^{t30813/t30813} (TU)	control	Long-pec	retina macrophage csf1ra expression decreased amount, abnormal	Fig. 2
trim33^{t30813/t30813} (TU)	control	Long-pec	retina macrophage decreased amount, abnormal	Fig. 2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
f12Tg	Tg(UAS:SEC-Hsa.ANXA5-YFP,myl7:RFP)	Transgenic Insertion
f13Tg	Tg(tbp:GAL4,myl7:Cerulean)	Transgenic Insertion
gl25Tg	Tg(mpeg1.1:GAL4FF)	Transgenic Insertion
i114Tg	Tg(mpx:GFP)	Transgenic Insertion
knu3Tg	Tg(elavl3:EGFP)	Transgenic Insertion
nz50Tg	Tg(lyz:DsRed2)	Transgenic Insertion
sd2Tg	Tg(gata1a:DsRed)	Transgenic Insertion
t30813		Unknown	trim33
tb222b		Point Mutation	trim33
ump2Tg	Tg(mpeg1.1:mCherryF)	Transgenic Insertion

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
trim33	MO4-trim33	MRPHLNO

Fish

Fish
f12Tg; f13Tg
f12Tg; f13Tg + MO4-trim33
f12Tg; f13Tg; sd2Tg
f12Tg; f13Tg; sd2Tg + MO4-trim33
i114Tg; ump2Tg
nz50Tg
trim33^t30813/+ (TU)
trim33^{t30813/t30813}; i114Tg; ump2Tg
trim33^{t30813/t30813}; nz50Tg
trim33^{t30813/t30813}; sd2Tg

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Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
DsRed	EFG	DsRed
DsRed2	EFG	DsRed2
EGFP	EFG	EGFP
GAL4	EFG	GAL4
GAL4FF	EFG	GAL4FF
GFP	EFG	GFP
mCherry	EFG	mCherry
RFP	EFG	RFP
YFP	EFG	YFP

Mapping

Demy et al., 2017 ZDB-PUB-170721-7 PMID:28724755

Trim33 / Tif1-γ is essential for macrophage and neutrophil mobilisation to developmental or inflammatory cues

Demy et al., 2017

ZDB-PUB-170721-7
PMID:28724755