Microfibril-associated glycoprotein 4 (MFAP4) regulates haematopoiesis in zebrafish
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 stru...
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Science::Biological sciences Developmental Biology Erythropoiesis Ong, Sheena L. M. de Vos, Ivo J. H. M. Meroshini, M. Poobalan, Yogavalli Dunn, Norris Ray Microfibril-associated glycoprotein 4 (MFAP4) regulates haematopoiesis in zebrafish |
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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. |
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Lee Kong Chian School of Medicine (LKCMedicine) |
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Lee Kong Chian School of Medicine (LKCMedicine) Ong, Sheena L. M. de Vos, Ivo J. H. M. Meroshini, M. Poobalan, Yogavalli Dunn, Norris Ray |
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Article |
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Ong, Sheena L. M. de Vos, Ivo J. H. M. Meroshini, M. Poobalan, Yogavalli Dunn, Norris Ray |
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Ong, Sheena L. M. |
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Microfibril-associated glycoprotein 4 (MFAP4) regulates haematopoiesis in zebrafish |
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Microfibril-associated glycoprotein 4 (MFAP4) regulates haematopoiesis in zebrafish |
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Microfibril-associated glycoprotein 4 (MFAP4) regulates haematopoiesis in zebrafish |
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Microfibril-associated glycoprotein 4 (MFAP4) regulates haematopoiesis in zebrafish |
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Microfibril-associated glycoprotein 4 (MFAP4) regulates haematopoiesis in zebrafish |
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microfibril-associated glycoprotein 4 (mfap4) regulates haematopoiesis in zebrafish |
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2021 |
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https://hdl.handle.net/10356/146072 |
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sg-ntu-dr.10356-1460722023-03-05T16:47:17Z Microfibril-associated glycoprotein 4 (MFAP4) regulates haematopoiesis in zebrafish Ong, Sheena L. M. de Vos, Ivo J. H. M. Meroshini, M. Poobalan, Yogavalli Dunn, Norris Ray Lee Kong Chian School of Medicine (LKCMedicine) Institute of Medical Biology, A*STAR Science::Biological sciences Developmental Biology Erythropoiesis 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. Skin Research Institute of Singapore (SRIS) Published version The authors acknowledge the invaluable input and technical assistance of Dr. Thomas J. Carney (Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore), Dr. Aniket Gore (NIH/NICHD, Bethesda, USA) and of Dr. Bruno Reversade (Institute of Medical Biology (A*STAR), Singapore) and members of his lab, particularly Dr. Serene Chng. We also wish to thank Dr. Karuna Sampath (Warwick University, UK) for her generous supply of advice, reagents and technical expertise throughout the course of this study. Finally, we wish to thank Dr. Sebastien Santini (Laboratoire Information Génomique et Structurale (IGS), UMR7256, Aix Marseille Université, CNRS) for the software used for phylogenetic analysis, and the Inkscape Team for the software used to create all figures. SLMO, MM, YP and NRD are supported by IMB core funds. IJHMdV is supported by the Skin Research Institute of Singapore (IAF-PP H17/01/a0004). 2021-01-25T08:51:07Z 2021-01-25T08:51:07Z 2020 Journal Article 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. https://dx.doi.org/10.1038/s41598-020-68792-8 2045-2322 https://hdl.handle.net/10356/146072 10.1038/s41598-020-68792-8 32678226 2-s2.0-85087963328 10 en IAF-PP H17/01/a0004 Scientific Reports © 2020 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. application/pdf |