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.

中文翻译：

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疾病相关的非肌肉肌球蛋白 IIA D1424N 杆结构域突变（但不是 R702C 运动结构域突变）破坏了小鼠眼晶状体纤维细胞排列和六边形堆积

小鼠晶状体是一种优秀的脊椎动物模型系统，用于研究组织形态发生和分化过程中的六边形细胞堆积和形状变化。晶状体由两种类型的细胞组成：上皮细胞和纤维细胞。在纤维细胞分化的起始过程中，晶状体上皮细胞从随机堆积的细胞转变为六角形且堆积的细胞，从而形成子午行细胞。子午行细胞进一步分化并伸长成新形成的纤维细胞，保持六边形细胞形状和有序堆积。在其他组织中，肌动球蛋白收缩性在上皮组织形态发生过程中调节细胞六边形堆积几何形状。在这里，我们使用小鼠晶状体作为模型来研究两种人类疾病相关的非肌肉肌球蛋白 IIA (NMIIA) 突变对纤维细胞形态发生和分化过程中晶状体细胞组织的影响。我们研究了具有 NMIIA-R702C 运动结构域或 NMIIA-D1424N 杆结构域突变的基因敲入杂合小鼠。我们观察到，虽然 NMIIA-R702C 的一个等位基因对晶状体子午行上皮细胞形状和堆积没有影响，但 NMIIA-D1424N 突变的一个等位基因可导致细胞六边形堆积的局部缺陷。同样，NMIIA-R702C 运动结构域突变的一个等位基因不会影响晶状体纤维细胞组织，而 NMIIA-D1424N 突变蛋白会破坏纤维细胞组织和堆积。我们的工作表明，与疾病相关的 NMIIA 杆结构域突变（D1424N 或 E1841K）会破坏小鼠晶状体纤维细胞的形态发生和分化。