PUBLICATION

Microfibril-associated glycoprotein 4 (Mfap4) regulates haematopoiesis in zebrafish

Authors

Ong, S.L.M., de Vos, I.J.H.M., Meroshini, M., Poobalan, Y., Dunn, N.R.

ID

ZDB-PUB-200719-10

Date

2020

Source

Scientific Reports 10: 11801 (Journal)

Registered Authors

Dunn, Norris Ray, Meroshini, M.

Keywords

none

MeSH Terms

Extracellular Matrix Proteins/genetics*
Extracellular Matrix Proteins/metabolism
Embryonic Development/genetics
Microfibrils/metabolism
Glycoproteins
Humans
Phenotype
Gene Expression Regulation
Carrier Proteins
Zebrafish/embryology
Zebrafish/genetics*
Zebrafish/metabolism
Gene Expression Profiling
Gene Deletion
Leukocyte Count
Animals
Hematopoiesis/genetics*

(all 17)

PubMed

32678226 Full text @ Sci. Rep.

Abstract

Microfibril-associated glycoprotein 4 (MFAP4) is an extracellular matrix protein belonging to the fibrinogen-related protein superfamily. MFAP4 is produced by vascular smooth muscle cells and is highly enriched in the blood vessels of the heart and lung, where it is thought to contribute to the structure and function of elastic fibers. Genetic studies in humans have implicated MFAP4 in the pathogenesis of Smith-Magenis syndrome, in which patients present with multiple congenital abnormalities and mental retardation, as well as in the severe cardiac malformation left-sided congenital heart disease. Comprehensive genetic analysis of the role of MFAP4 orthologues in model organisms during development and tissue homeostasis is however lacking. Here, we demonstrate that zebrafish mfap4 transcripts are detected embryonically, resolving to the macrophage lineage by 24 h post fertilization. mfap4 null mutant zebrafish are unexpectedly viable and fertile, without ostensible phenotypes. However, tail fin amputation assays reveal that mfap4 mutants have reduced numbers of macrophages, with a concomitant increase in neutrophilic granulocytes, although recruitment of both cell types to the site of injury was unaffected. Molecular analyses suggest that loss of Mfap4 alters the balance between myeloid and lymphoid lineages during both primitive and definitive haematopoiesis, which could significantly impact the downstream function of the immune system.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
cpa5	mfap4.2^imb5/imb5	standard conditions	Days 7-13	granulocyte	RTPCR	Figure 5
EGFP	gl22Tg/gl22Tg	standard conditions	Protruding-mouth	caudal fin neutrophil	IFL	Figure 4
EGFP	gl22Tg/gl22Tg	amputation: caudal fin	Protruding-mouth	regenerating fin neutrophil	IFL	Figure 4
EGFP	mfap4.2^imb5/imb5; gl22Tg/gl22Tg	standard conditions	Protruding-mouth	caudal fin neutrophil	IFL	Figure 4
EGFP	mfap4.2^imb5/imb5; gl22Tg/gl22Tg	amputation: caudal fin	Protruding-mouth	macrophage	IFL	Figure 3
EGFP	mfap4.2^imb5/imb5; gl22Tg/gl22Tg	standard conditions	Protruding-mouth	macrophage	IFL	Figure 3
EGFP	mfap4.2^imb5/imb5; gl22Tg/gl22Tg	amputation: caudal fin	Protruding-mouth	regenerating fin macrophage	IFL	Figure 3
EGFP	mfap4.2^imb5/imb5; gl22Tg/gl22Tg	amputation: caudal fin	Protruding-mouth	regenerating fin neutrophil	IFL	Figure 4
gata1a	mfap4.2^imb5/imb5	standard conditions	10-13 somites to 14-19 somites	erythroid progenitor cell	RTPCR	Figure 5
gata1a	mfap4.2^imb5/imb5	standard conditions	Days 7-13	erythroid progenitor cell	RTPCR	Figure 5

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
mfap4.2^imb5/imb5	standard conditions	10-13 somites to 14-19 somites	common myeloid progenitor spi1b expression increased amount, abnormal	Figure 5
mfap4.2^imb5/imb5	standard conditions	10-13 somites to 14-19 somites	erythroid progenitor cell gata1a expression decreased amount, abnormal	Figure 5
mfap4.2^imb5/imb5	standard conditions	10-13 somites to 14-19 somites	macrophage lcp1 expression increased amount, abnormal	Figure 5
mfap4.2^imb5/imb5	standard conditions	Prim-5	whole organism mfap4.2 expression decreased amount, abnormal	Figure 2
mfap4.2^imb5/imb5	standard conditions	Long-pec	whole organism mfap4.2 expression decreased amount, abnormal	Figure 2
mfap4.2^imb5/imb5	standard conditions	Protruding-mouth	macrophage mfap4.2 expression decreased amount, abnormal	Figure 2
mfap4.2^imb5/imb5	standard conditions	Protruding-mouth	whole organism mfap4.2 expression decreased amount, abnormal	Figure 2
mfap4.2^imb5/imb5	standard conditions	Days 7-13	granulocyte cpa5 expression decreased amount, abnormal	Figure 5
mfap4.2^imb5/imb5	standard conditions	Days 7-13	granulocyte monocyte progenitor cell spi1b expression decreased amount, abnormal	Figure 5
mfap4.2^imb5/imb5	standard conditions	Days 7-13	hematopoietic multipotent progenitor cell gata2a expression decreased amount, abnormal	Figure 5

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
gl22Tg	Tg(mpeg1:EGFP)	Transgenic Insertion
imb5		Small Deletion	mfap4.2

Human Disease / Model

Human Disease	Fish	Conditions	Evidence
Smith-Magenis syndrome	mfap4.2^imb5/imb5	standard conditions	TAS

Sequence Targeting Reagents

Target	Reagent	Reagent Type
mfap4.1	CRISPR1-mfap4	CRISPR
mfap4.1	CRISPR2-mfap4	CRISPR
mfap4.2	CRISPR1-mfap4	CRISPR
mfap4.2	CRISPR2-mfap4	CRISPR
mfap4.3	CRISPR1-mfap4	CRISPR
mfap4.3	CRISPR2-mfap4	CRISPR

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Fish

Fish
gl22Tg/gl22Tg
mfap4.2^imb5/imb5
mfap4.2^imb5/imb5
mfap4.2^imb5/imb5; gl22Tg/gl22Tg
WT

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab5-mpx	polyclonal	mpx	IgG	Rabbit

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Ong et al., 2020 ZDB-PUB-200719-10 PMID:32678226

Microfibril-associated glycoprotein 4 (Mfap4) regulates haematopoiesis in zebrafish

Ong et al., 2020

ZDB-PUB-200719-10
PMID:32678226