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
-
- Animals
- Carrier Proteins
- Embryonic Development/genetics
- Extracellular Matrix Proteins/genetics*
- Extracellular Matrix Proteins/metabolism
- Gene Deletion
- Gene Expression Profiling
- Gene Expression Regulation
- Glycoproteins
- Hematopoiesis/genetics*
- Humans
- Leukocyte Count
- Microfibrils/metabolism
- Phenotype
- Zebrafish/embryology
- Zebrafish/genetics*
- Zebrafish/metabolism
- PubMed
- 32678226 Full text @ Sci. Rep.
Citation
Ong, S.L.M., de Vos, I.J.H.M., Meroshini, M., Poobalan, Y., Dunn, N.R. (2020) Microfibril-associated glycoprotein 4 (Mfap4) regulates haematopoiesis in zebrafish. Scientific Reports. 10:11801.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping