Lancaster Courtney, Manhart Angelika, Pichaud Franck
Cell Biology of Tissue Architecture and Physiology Group, Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK.
Faculty of Mathematics, University of Vienna, Vienna 1090, Austria; Department of Mathematics, University College London, London WC1E 6BT, UK.
Curr Biol. 2025 Jul 21;35(14):3287-3302.e3. doi: 10.1016/j.cub.2025.05.048. Epub 2025 Jun 17.
During development, tissues undergo morphogenesis to achieve their final form. This process relies on coordinated cell shape changes, which have predominantly been studied in one plane, at the apical (top) surface of developing tissues. However, tissues are three dimensional, often exhibiting deformations along multiple axes. To understand how morphogenesis is coordinated across tissue axes, we used the genetically amenable Drosophila retina, a curved, dome-shaped epithelium, as a model system. Using intravital imaging, we found that retinal curvature is induced early in development. Modeling early retinal development with a vertex model suggests that this curvature arises from differential planar growth between the apical and basal tissue surfaces. In addition, mechanical perturbation experiments revealed that inside-out fluid pressure plays a crucial role in promoting this curvature. Further combining computational modeling, genetic perturbations, and force-inference experiments, we demonstrate that uniform thickening of the curved retinal epithelium requires coordination of two key processes: growth, promoting cell elongation along the apical-basal axis of the tissue, and basal surface contraction. Remarkably, inhibiting basal surface contraction-both in silico and through genetic manipulations targeting the basal surface receptor integrin and non-muscle myosin-II-prevented cell elongation. We conclude that thickening of a curved epithelium, like the Drosophila retina, requires both integrin and non-muscle myosin-II to coordinate basal surface contraction and cell growth along the apical-basal axis of the tissue.
在发育过程中，组织会经历形态发生以形成其最终形态。这个过程依赖于协调的细胞形状变化，而这些变化主要是在发育中组织的顶端（顶部）表面的一个平面上进行研究的。然而，组织是三维的，常常沿多个轴表现出变形。为了了解形态发生是如何在组织轴之间协调的，我们使用了易于进行基因操作的果蝇视网膜，这是一种弯曲的、穹顶状的上皮组织，作为一个模型系统。通过活体成像，我们发现视网膜曲率在发育早期就被诱导产生。用顶点模型对早期视网膜发育进行建模表明，这种曲率源于顶端和基底组织表面之间不同的平面生长。此外，机械扰动实验表明，由内向外的流体压力在促进这种曲率方面起着关键作用。进一步结合计算建模、基因扰动和力推断实验，我们证明弯曲的视网膜上皮组织的均匀增厚需要两个关键过程的协调：生长，促进细胞沿组织的顶端 - 基底轴伸长，以及基底表面收缩。值得注意的是，无论是在计算机模拟中还是通过针对基底表面受体整合素和非肌肉肌球蛋白 II 的基因操作来抑制基底表面收缩，都会阻止细胞伸长。我们得出结论，像果蝇视网膜这样的弯曲上皮组织的增厚需要整合素和非肌肉肌球蛋白 II 来协调基底表面收缩和细胞沿组织顶端 - 基底轴的生长。
