Myh9b is a Critical Non-muscle Myosin II Encoding Gene That Interacts with Myh9a and Myh10 During Zebrafish Development in Both Compensatory and Redundant Pathways

Overview

Journal G3 (Bethesda)

Publisher Oxford University Press

Specialties Genetics
Molecular Biology

Date 2024 Nov 6

PMID 39503257

Authors

Laura A Rolfs

Elizabeth J Falat

Jennifer H Gutzman

Affiliations

Soon will be listed here.

Abstract

Non-muscle myosin (NMII) motor proteins have diverse developmental functions due to their roles in cell shape changes, cell migration, and cell adhesion. Zebrafish are an ideal vertebrate model system to study the NMII encoding myh genes and proteins due to high sequence homology, established gene editing tools, and rapid ex utero development. In humans, mutations in the NMII encoding MYH genes can lead to abnormal developmental processes and disease. This study utilized zebrafish myh9a, myh9b, and myh10 null mutants to examine potential genetic interactions and roles for each gene in development. It was determined that the myh9b gene is the most critical NMII encoding gene, as myh9b mutants develop pericardial edema and have a partially penetrant lethal phenotype, which was not observed in the other myh mutants. This study also established that genetic interactions occur between the zebrafish myh9a, myh9b, and myh10 genes where myh9b is required for the expression of both myh9a and myh10, and myh10 is required for the expression of myh9b. Additionally, protein analyses suggested that enhanced NMII protein stability in some mutant backgrounds may play a role in compensation. Finally, double mutant studies revealed different and more severe phenotypes at earlier time points than single mutants, suggesting roles for tissue specific genetic redundancy, and in some genotypes, haploinsufficiency. These mutants are the first in vivo models allowing for the study of complete loss of the NMIIA and NMIIB proteins, establishing them as valuable tools to elucidate the role of NMII encoding myh genes in development and disease.

References

Seri M, Cusano R, Gangarossa S, Caridi G, Bordo D, Lo Nigro C . Mutations in MYH9 result in the May-Hegglin anomaly, and Fechtner and Sebastian syndromes. The May-Heggllin/Fechtner Syndrome Consortium. Nat Genet. 2000; 26(1):103-5. DOI: 10.1038/79063. View

Kim B, Kim A, Han J, Lee C, Oh D, Choi B . Discovery of MYH14 as an important and unique deafness gene causing prelingually severe autosomal dominant nonsyndromic hearing loss. J Gene Med. 2017; 19(4). DOI: 10.1002/jgm.2950. View

Franke J, Montague R, Rickoll W, Kiehart D . An MYH9 human disease model in flies: site-directed mutagenesis of the Drosophila non-muscle myosin II results in hypomorphic alleles with dominant character. Hum Mol Genet. 2007; 16(24):3160-73. DOI: 10.1093/hmg/ddm279. View

Hunter G, He L, Perrimon N, Charras G, Giniger E, Baum B . A role for actomyosin contractility in Notch signaling. BMC Biol. 2019; 17(1):12. PMC: 6369551. DOI: 10.1186/s12915-019-0625-9. View

Ma X, Adelstein R . A point mutation in Myh10 causes major defects in heart development and body wall closure. Circ Cardiovasc Genet. 2014; 7(3):257-65. PMC: 4106703. DOI: 10.1161/CIRCGENETICS.113.000455. View

Zhang Y, Conti M, Malide D, Dong F, Wang A, Shmist Y . Mouse models of MYH9-related disease: mutations in nonmuscle myosin II-A. Blood. 2011; 119(1):238-50. PMC: 3251230. DOI: 10.1182/blood-2011-06-358853. View

Beach J, Shao L, Remmert K, Li D, Betzig E, Hammer 3rd J . Nonmuscle Myosin II Isoforms Coassemble in Living Cells. Curr Biol. 2018; 25(3):402. DOI: 10.1016/j.cub.2015.01.028. View

Balaghi N, Erdemci-Tandogan G, McFaul C, Fernandez-Gonzalez R . Myosin waves and a mechanical asymmetry guide the oscillatory migration of Drosophila cardiac progenitors. Dev Cell. 2023; 58(14):1299-1313.e5. DOI: 10.1016/j.devcel.2023.05.005. View

Halder D, Mallick D, Chatterjee A, Jana S . Nonmuscle Myosin II in cancer cell migration and mechanotransduction. Int J Biochem Cell Biol. 2021; 139:106058. DOI: 10.1016/j.biocel.2021.106058. View

10.

Hentschel D, Park K, Cilenti L, Zervos A, Drummond I, Bonventre J . Acute renal failure in zebrafish: a novel system to study a complex disease. Am J Physiol Renal Physiol. 2004; 288(5):F923-9. DOI: 10.1152/ajprenal.00386.2004. View

11.

Koressaar T, Lepamets M, Kaplinski L, Raime K, Andreson R, Remm M . Primer3_masker: integrating masking of template sequence with primer design software. Bioinformatics. 2018; 34(11):1937-1938. DOI: 10.1093/bioinformatics/bty036. View

12.

Young P, Richman A, KETCHUM A, Kiehart D . Morphogenesis in Drosophila requires nonmuscle myosin heavy chain function. Genes Dev. 1993; 7(1):29-41. DOI: 10.1101/gad.7.1.29. View

13.

Kelley M, Jawien W, Ortel T, Korczak J . Mutation of MYH9, encoding non-muscle myosin heavy chain A, in May-Hegglin anomaly. Nat Genet. 2000; 26(1):106-8. DOI: 10.1038/79069. View

14.

Donaudy F, Snoeckx R, Pfister M, Zenner H, Blin N, DI Stazio M . Nonmuscle myosin heavy-chain gene MYH14 is expressed in cochlea and mutated in patients affected by autosomal dominant hearing impairment (DFNA4). Am J Hum Genet. 2004; 74(4):770-6. PMC: 1181955. DOI: 10.1086/383285. View

15.

Liu J, Maduzia L, Shirayama M, Mello C . NMY-2 maintains cellular asymmetry and cell boundaries, and promotes a SRC-dependent asymmetric cell division. Dev Biol. 2010; 339(2):366-73. PMC: 2903000. DOI: 10.1016/j.ydbio.2009.12.041. View

16.

Pecci A, Canobbio I, Balduini A, Stefanini L, Cisterna B, Marseglia C . Pathogenetic mechanisms of hematological abnormalities of patients with MYH9 mutations. Hum Mol Genet. 2005; 14(21):3169-78. DOI: 10.1093/hmg/ddi344. View

17.

Garrido-Casado M, Asensio-Juarez G, Vicente-Manzanares M . Nonmuscle Myosin II Regulation Directs Its Multiple Roles in Cell Migration and Division. Annu Rev Cell Dev Biol. 2021; 37:285-310. DOI: 10.1146/annurev-cellbio-042721-105528. View

18.

Hegarty J, Yang H, Chi N . UBIAD1-mediated vitamin K2 synthesis is required for vascular endothelial cell survival and development. Development. 2013; 140(8):1713-9. PMC: 3621489. DOI: 10.1242/dev.093112. View

19.

Huang M, Akerberg A, Zhang X, Yoon H, Joshi S, Hallinan C . Intrinsic myocardial defects underlie an Rbfox-deficient zebrafish model of hypoplastic left heart syndrome. Nat Commun. 2022; 13(1):5877. PMC: 9534849. DOI: 10.1038/s41467-022-32982-x. View

20.

Dulyaninova N, Bresnick A . The heavy chain has its day: regulation of myosin-II assembly. Bioarchitecture. 2013; 3(4):77-85. PMC: 4201608. DOI: 10.4161/bioa.26133. View