Abstract

We investigated the physiological functions of Myo10 (myosin X) using Myo10 reporter knockout (Myo10tm2) mice. Full-length (motorized) Myo10 protein was deleted, but the brain-specific headless (Hdl) isoform (Hdl-Myo10) was still expressed in homozygous mutants. In vitro, we confirmed that Hdl-Myo10 does not induce filopodia, but it strongly localized to the plasma membrane independent of the MyTH4-FERM domain. Filopodia-inducing Myo10 is implicated in axon guidance and mice lacking the Myo10 cargo protein DCC (deleted in colorectal cancer) have severe commissural defects, whereas MRI (magnetic resonance imaging) of isolated brains revealed intact commissures in Myo10tm2/tm2 mice. However, reminiscent of Waardenburg syndrome, a neural crest disorder, Myo10tm2/tm2 mice exhibited pigmentation defects (white belly spots) and simple syndactyly with high penetrance (>95%), and 24% of mutant embryos developed exencephalus, a neural tube closure defect. Furthermore, Myo10tm2/tm2 mice consistently displayed bilateral persistence of the hyaloid vasculature, revealed by MRI and retinal whole-mount preparations. In principle, impaired tissue clearance could contribute to persistence of hyaloid vasculature and syndactyly. However, Myo10-deficient macrophages exhibited no defects in the phagocytosis of apoptotic or IgG-opsonized cells. RNA sequence analysis showed that Myo10 was the most strongly expressed unconventional myosin in retinal vascular endothelial cells and expression levels increased 4-fold between P6 and P15, when vertical sprouting angiogenesis gives rise to deeper layers. Nevertheless, imaging of isolated adult mutant retinas did not reveal vascularization defects. In summary, Myo10 is important for both prenatal (neural tube closure and digit formation) and postnatal development (hyaloid regression, but not retinal vascularization).

Details

Title
Phenotypic analysis of Myo10 knockout (Myo10tm2/tm2) mice lacking full-length (motorized) but not brain-specific headless myosin X
Author
Bachg, Anne C 1 ; Horsthemke Markus 1 ; Skryabin, Boris V 2 ; Klasen, Tim 3 ; Nagelmann Nina 3 ; Faber, Cornelius 3   VIAFID ORCID Logo  ; Woodham, Emma 4 ; Machesky, Laura M 4 ; Bachg Sandra 5 ; Stange, Richard 5 ; Hyun-Woo, Jeong 6   VIAFID ORCID Logo  ; Adams, Ralf H 6   VIAFID ORCID Logo  ; Bähler, Martin 1 ; Hanley, Peter J 1 

 Westfälische Wilhelms-Universität Münster, Institut für Molekulare Zellbiologie, Münster, Germany (GRID:grid.5949.1) (ISNI:0000 0001 2172 9288) 
 Transgenic Animal and Genetic Engineering Models (TRAM), Westfälische Wilhelms-Universität Münster, Department of Medicine, Münster, Germany (GRID:grid.5949.1) (ISNI:0000 0001 2172 9288) 
 Westfälische Wilhelms-Universität Münster, Department of Clinical Radiology, Münster, Germany (GRID:grid.5949.1) (ISNI:0000 0001 2172 9288) 
 Cancer Research UK Beatson Institute, Glasgow University College of Medical, Veterinary and Life Sciences Garscube Estate, Glasgow, United Kingdom (GRID:grid.23636.32) (ISNI:0000 0000 8821 5196) 
 Institute of Musculoskeletal Medicine (IMM), University Hospital Münster, Department of Regenerative Musculoskeletal Medicine, Münster, Germany (GRID:grid.16149.3b) (ISNI:0000 0004 0551 4246) 
 Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, Max Planck Institute for Molecular Biomedicine, Münster, Germany (GRID:grid.5949.1) (ISNI:0000 0001 2172 9288) 
Publication year
2019
Publication date
Jan 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2344521608
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.