Developmental Neurobiology Unit, Okinawa Institute of Science and Technology Graduate University, Onna, Okinawa 904-0495, Japan.
Save Sight Institute, The University of Sydney, Sydney, NSW 2000, Australia.
Development. 2024 Feb 1;151(3). doi: 10.1242/dev.202123. Epub 2024 Feb 7.
The spheroidal shape of the eye lens is crucial for precise light focusing onto the retina. This shape is determined by concentrically aligned, convexly elongated lens fiber cells along the anterior and posterior axis of the lens. Upon differentiation at the lens equator, the fiber cells increase in height as their apical and basal tips migrate towards the anterior and posterior poles, respectively. The forces driving this elongation and migration remain unclear. We found that, in the mouse lens, membrane protrusions or lamellipodia are observed only in the maturing fibers undergoing cell curve conversion, indicating that lamellipodium formation is not the primary driver of earlier fiber migration. We demonstrated that elevated levels of fibroblast growth factor (FGF) suppressed the extension of Rac-dependent protrusions, suggesting changes in the activity of FGF controlling Rac activity, switching to lamellipodium-driven migration. Inhibitors of ROCK, myosin and actin reduced the height of both early and later fibers, indicating that elongation of these fibers relies on actomyosin contractility. Consistent with this, active RhoA was detected throughout these fibers. Given that FGF promotes fiber elongation, we propose that it does so through regulation of Rho activity.
眼球晶状体的球形形状对于将光线精确聚焦到视网膜上至关重要。这种形状是由沿着晶状体前后轴同心排列的凸形伸长的晶状体纤维细胞决定的。在晶状体赤道处分化时，纤维细胞的高度增加，其顶端和基底尖端分别向前后极迁移。推动这种伸长和迁移的力尚不清楚。我们发现，在小鼠晶状体中，只有在经历细胞曲线转换的成熟纤维中才观察到膜突或片状伪足，表明片状伪足的形成不是早期纤维迁移的主要驱动因素。我们证明，成纤维细胞生长因子 (FGF) 水平升高抑制了 Rac 依赖性突起的延伸，这表明 FGF 控制 Rac 活性的活性发生变化，转向片状伪足驱动的迁移。ROCK、肌球蛋白和肌动蛋白抑制剂降低了早期和晚期纤维的高度，表明这些纤维的伸长依赖于肌动球蛋白的收缩性。与这一致，在这些纤维中检测到活性 RhoA。鉴于 FGF 促进纤维伸长，我们提出它通过调节 Rho 活性来实现。
