Department of Biochemistry, University of Geneva, 30 Quai Ernest-Ansermet, 1211 Geneva 4, Switzerland.
Development. 2014 May;141(10):2014-23. doi: 10.1242/dev.104240.
Tissue homeostasis is maintained by adult stem cells, which self-renew and give rise to differentiating cells. The generation of daughter cells with different fates is mediated by signalling molecules coming from an external niche or being asymmetrically dispatched between the two daughters upon stem cell mitosis. In the adult Drosophila midgut, the intestinal stem cell (ISC) divides to generate a new ISC and an enteroblast (EB) differentiating daughter. Notch signalling activity restricted to the EB regulates intestinal cell fate decision. Here, we show that ISCs divide asymmetrically, and Sara endosomes in ISCs are specifically dispatched to the presumptive EB. During ISC mitosis, Notch and Delta traffic through Sara endosomes, thereby contributing to Notch signalling bias, as revealed in Sara mutants: Sara itself contributes to the control of the ISC asymmetric division. Our data uncover an intrinsic endosomal mechanism during ISC mitosis, which participates in the maintenance of the adult intestinal lineage.
组织稳态由成年干细胞维持,这些干细胞自我更新并产生分化细胞。来自外部生态位的信号分子或在干细胞有丝分裂过程中在两个子细胞之间不对称分配,介导具有不同命运的子细胞的产生。在成年果蝇中肠中,肠干细胞(ISC)分裂产生新的 ISC 和分化的肠母细胞(EB)。仅限于 EB 的 Notch 信号活性调节肠细胞命运决定。在这里,我们表明 ISC 不对称分裂,并且 ISC 中的 Sara 内体被特异性分配到假定的 EB。在 ISC 有丝分裂过程中,Notch 和 Delta 通过 Sara 内体运输,从而导致 Notch 信号偏向,如在 Sara 突变体中所示:Sara 本身有助于控制 ISC 的不对称分裂。我们的数据揭示了 ISC 有丝分裂过程中的内在内体机制,该机制参与维持成年肠谱系。