Institut Pasteur, Paris, France.
UMR3738, Centre National de la Recherche Scientifique, Paris, France.
J Cell Biol. 2020 Nov 2;219(11). doi: 10.1083/jcb.202005035.
Many tissues are produced by specialized progenitor cells emanating from epithelia via epithelial-to-mesenchymal transition (EMT). Most studies have so far focused on EMT involving single or isolated groups of cells. Here we describe an EMT-like process that requires tissue-level coordination. This EMT-like process occurs along a continuous front in the Drosophila optic lobe neuroepithelium to produce neural stem cells (NSCs). We find that emerging NSCs remain epithelial and apically constrict before dividing asymmetrically to produce neurons. Apical constriction is associated with contractile myosin pulses and involves RhoGEF3 and down-regulation of the Crumbs complex by the E3 ubiquitin ligase Neuralized. Anisotropy in Crumbs complex levels also results in accumulation of junctional myosin. Disrupting the regulation of Crumbs by Neuralized lowered junctional myosin and led to imprecision in the integration of emerging NSCs into the front. Thus, Neuralized promotes smooth progression of the differentiation front by coupling epithelium remodeling at the tissue level with NSC fate acquisition.
许多组织是由上皮细胞通过上皮-间充质转化（EMT）产生的专门祖细胞产生的。到目前为止，大多数研究都集中在涉及单个或孤立细胞群的 EMT 上。在这里，我们描述了一个需要组织水平协调的 EMT 样过程。这个 EMT 样过程沿着果蝇脑垂体神经上皮的连续前缘发生，产生神经干细胞（NSC）。我们发现，新出现的 NSCs 在不对称分裂产生神经元之前仍然保持上皮细胞状态并在顶端收缩。顶端收缩与收缩性肌球蛋白脉冲有关，涉及 RhoGEF3 和 E3 泛素连接酶 Neuralized 下调 Crumbs 复合物。Crumbs 复合物水平的各向异性也导致了连接肌球蛋白的积累。Neuralized 对 Crumbs 调节的破坏降低了连接肌球蛋白，导致新出现的 NSCs 在前缘的整合不准确。因此，Neuralized 通过将组织水平的上皮重塑与 NSC 命运获取相结合，促进了分化前缘的顺利推进。
