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. 2024 Dec;81(12):789-805.
doi: 10.1002/cm.21853. Epub 2024 Mar 22.

Disease-related non-muscle myosin IIA D1424N rod domain mutation, but not R702C motor domain mutation, disrupts mouse ocular lens fiber cell alignment and hexagonal packing

Sadia T Islam  1 , Sepideh Cheheltani  1 , Catherine Cheng  2   3 , Velia M Fowler  1   3
Affiliations

Disease-related non-muscle myosin IIA D1424N rod domain mutation, but not R702C motor domain mutation, disrupts mouse ocular lens fiber cell alignment and hexagonal packing

Sadia T Islam et al. Cytoskeleton (Hoboken). 2024 Dec.

Abstract

The mouse ocular lens is an excellent vertebrate model system for studying hexagonal cell packing and shape changes during tissue morphogenesis and differentiation. The lens is composed of two types of cells, epithelial and fiber cells. During the initiation of fiber cell differentiation, lens epithelial cells transform from randomly packed cells to hexagonally shaped and packed cells to form meridional row cells. The meridional row cells further differentiate and elongate into newly formed fiber cells that maintain hexagonal cell shape and ordered packing. In other tissues, actomyosin contractility regulates cell hexagonal packing geometry during epithelial tissue morphogenesis. Here, we use the mouse lens as a model to study the effect of two human disease-related non-muscle myosin IIA (NMIIA) mutations on lens cellular organization during fiber cell morphogenesis and differentiation. We studied genetic knock-in heterozygous mice with NMIIA-R702C motor domain or NMIIA-D1424N rod domain mutations. We observed that while one allele of NMIIA-R702C has no impact on lens meridional row epithelial cell shape and packing, one allele of the NMIIA-D1424N mutation can cause localized defects in cell hexagonal packing. Similarly, one allele of NMIIA-R702C motor domain mutation does not affect lens fiber cell organization while the NMIIA-D1424N mutant proteins disrupt fiber cell organization and packing. Our work demonstrates that disease-related NMIIA rod domain mutations (D1424N or E1841K) disrupt mouse lens fiber cell morphogenesis and differentiation.

Keywords: Myh9; epithelial tissue morphogenesis; hexagon cell shape; honeycomb packing; lens epithelial cell; lens meridional rows.

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