Cell Biology of Tissue Architecture and Physiology. Laboratory for Molecular Cell Biology (LMCB), University College London, London, United Kingdom.
PLoS Biol. 2024 Sep 3;22(9):e3002783. doi: 10.1371/journal.pbio.3002783. eCollection 2024 Sep.
Cell shape remodeling is a principal driver of epithelial tissue morphogenesis. While progress continues to be made in our understanding of the pathways that control the apical (top) geometry of epithelial cells, we know comparatively little about those that control cell basal (bottom) geometry. To examine this, we used the Drosophila ommatidium, which is the basic visual unit of the compound eye. The ommatidium is shaped as a hexagonal prism, and generating this 3D structure requires ommatidial cells to adopt specific apical and basal polygonal geometries. Using this model system, we find that generating cell type-specific basal geometries starts with patterning of the basal extracellular matrix, whereby Laminin accumulates at discrete locations across the basal surface of the retina. We find the Dystroglycan receptor complex (DGC) is required for this patterning by promoting localized Laminin accumulation at the basal surface of cells. Moreover, our results reveal that localized accumulation of Laminin and the DGC are required for directing Integrin adhesion. This induces cell basal geometry remodeling by anchoring the basal surface of cells to the extracellular matrix at specific, Laminin-rich locations. We propose that patterning of a basal extracellular matrix by generating discrete Laminin domains can direct Integrin adhesion to induce cell shape remodeling in epithelial morphogenesis.
细胞形状重塑是上皮组织形态发生的主要驱动因素。虽然我们在理解控制上皮细胞顶端(顶部)几何形状的途径方面不断取得进展,但我们对控制细胞基底(底部)几何形状的途径知之甚少。为了研究这一点,我们使用了果蝇小眼,它是复眼的基本视觉单位。小眼呈六棱柱形,生成这种 3D 结构需要小眼细胞采用特定的顶端和基底多边形几何形状。使用这个模型系统,我们发现产生细胞类型特异性基底几何形状始于基底细胞外基质的模式形成,其中层粘连蛋白在视网膜的基底表面上以离散的位置积累。我们发现 Dystroglycan 受体复合物(DGC)通过促进细胞基底表面的局部层粘连蛋白积累来促进这种模式形成。此外,我们的结果表明,层粘连蛋白和 DGC 的局部积累对于指导整合素粘附是必需的。这通过将细胞的基底表面固定在特定的富含层粘连蛋白的位置,从而锚定细胞外基质,来诱导细胞基底几何形状重塑。我们提出,通过生成离散的层粘连蛋白域来对基底细胞外基质进行图案化,可以指导整合素粘附,从而诱导上皮形态发生中的细胞形状重塑。