Affiliation:
1. Department of Biological Sciences University of Delaware Newark Delaware USA
2. School of Optometry and Vision Science Program Indiana University Bloomington Indiana USA
3. Department of Molecular Medicine, The Scripps Research Institute La Jolla California USA
Abstract
AbstractThe 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.
Funder
University of Delaware
National Institute of General Medical Sciences
Delaware IDeA Network of Biomedical Research Excellence
National Eye Institute
National Institutes of Health
Cited by
1 articles.
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