Non-muscle myosin IIB (Myh10) is required for epicardial function and coronary vessel formation during mammalian development.

RIDGE, Liam A., MITCHELL, Karen, AL-ANBAKI, Ali, SHAIKH QURESHI, Wasay Mohiuddin, STEPHEN, Louise A, TENIN, Gennadiy, LU, Yinhui, LUPU, Irina-Elena, CLOWES, Christopher, ROBERTSON, Abigail, BARNES, Emma, WRIGHT, Jayne A, KEAVNEY, Bernard, EHLER, Elisabeth, LOVELL, Simon C, KADLER, Karl E and HENTGES, Kathryn E (2017). Non-muscle myosin IIB (Myh10) is required for epicardial function and coronary vessel formation during mammalian development. PLOS Genetics, 13 (10), e1007068.

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Abstract

The coronary vasculature is an essential vessel network providing the blood supply to the heart. Disruptions in coronary blood flow contribute to cardiac disease, a major cause of premature death worldwide. The generation of treatments for cardiovascular disease will be aided by a deeper understanding of the developmental processes that underpin coronary vessel formation. From an ENU mutagenesis screen, we have isolated a mouse mutant displaying embryonic hydrocephalus and cardiac defects (EHC). Positional cloning and candidate gene analysis revealed that the EHC phenotype results from a point mutation in a splice donor site of the Myh10 gene, which encodes NMHC IIB. Complementation testing confirmed that the Myh10 mutation causes the EHC phenotype. Characterisation of the EHC cardiac defects revealed abnormalities in myocardial development, consistent with observations from previously generated NMHC IIB null mouse lines. Analysis of the EHC mutant hearts also identified defects in the formation of the coronary vasculature. We attribute the coronary vessel abnormalities to defective epicardial cell function, as the EHC epicardium displays an abnormal cell morphology, reduced capacity to undergo epithelial-mesenchymal transition (EMT), and impaired migration of epicardial-derived cells (EPDCs) into the myocardium. Our studies on the EHC mutant demonstrate a requirement for NMHC IIB in epicardial function and coronary vessel formation, highlighting the importance of this protein in cardiac development and ultimately, embryonic survival.

Item Type:	Article
Uncontrolled Keywords:	0604 Genetics; Developmental Biology; 3105 Genetics
Identification Number:	https://doi.org/10.1371/journal.pgen.1007068
Page Range:	e1007068
SWORD Depositor:	Symplectic Elements
Depositing User:	Symplectic Elements
Date Deposited:	07 Jun 2023 16:25
Last Modified:	11 Oct 2023 14:16
URI:	https://shura.shu.ac.uk/id/eprint/31585

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