Ferme Lucrezia C, Ryan Allyson Q, Haase Robert, Modes Carl D, Norden Caren
Gulbenkian Institute for Molecular Medicine, rua da Quinta Grande 6, 2780-156 Oeiras, Portugal (formerly Instituto Gulbenkian de Ciência, IGC).
Max-Planck Institute for Molecular Cell Biology and Genetics, MPI-CBG, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Sci Adv. 2025 May 9;11(19):eadu6843. doi: 10.1126/sciadv.adu6843.
Correct organogenesis depends on the timely coordination of developmental processes, such as cell proliferation, differentiation, and migration. This coordination is particularly critical in crowded tissues, such as pseudostratified epithelia (PSE) that are often found as organ precursors. They are composed of elongated epithelial cells with densely packed nuclei aligned along the apicobasal axis. While cell cycle-dependent nuclear movements in PSE are well studied, less is known about how nuclear packing influences tissue morphogenesis. To investigate this, we analyzed nuclear shapes, sizes, and neighborhood statistics in zebrafish neuroepithelia, focusing on the retinal PSE. We found that nuclei exhibit elongated shapes and biaxial nematic-like orientational order but remain positionally disordered. During retinal development, nuclear packing density increases, approaching theoretical limits. This occurs when the tissue transitions to a laminated structure and nuclear shapes are remodeled. Timely neurogenesis is critical as failure to initiate neurogenesis leads to tissue deformations. These findings highlight the influence of nuclear shape and positioning for organ morphogenesis.
正确的器官发生依赖于发育过程的及时协调，如细胞增殖、分化和迁移。这种协调在拥挤的组织中尤为关键，例如常作为器官前体的假复层上皮（PSE）。它们由细长的上皮细胞组成，细胞核沿顶-基轴密集排列。虽然PSE中依赖细胞周期的核运动已得到充分研究，但关于核堆积如何影响组织形态发生却知之甚少。为了研究这一点，我们分析了斑马鱼神经上皮中的核形状、大小和邻域统计数据，重点关注视网膜PSE。我们发现细胞核呈现细长形状和双轴向列型取向有序，但位置上是无序的。在视网膜发育过程中，核堆积密度增加，接近理论极限。这发生在组织转变为分层结构且核形状重塑时。及时的神经发生至关重要，因为未能启动神经发生会导致组织变形。这些发现突出了核形状和定位对器官形态发生的影响。
