Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
PLoS Genet. 2021 Jun 7;17(6):e1009146. doi: 10.1371/journal.pgen.1009146. eCollection 2021 Jun.
The Hippo pathway is an important regulator of organ growth and cell fate. In the R8 photoreceptor cells of the Drosophila melanogaster eye, the Hippo pathway controls the fate choice between one of two subtypes that express either the blue light-sensitive Rhodopsin 5 (Hippo inactive R8 subtype) or the green light-sensitive Rhodopsin 6 (Hippo active R8 subtype). The degree to which the mechanism of Hippo signal transduction and the proteins that mediate it are conserved in organ growth and R8 cell fate choice is currently unclear. Here, we identify Crumbs and the apical spectrin cytoskeleton as regulators of R8 cell fate. By contrast, other proteins that influence Hippo-dependent organ growth, such as the basolateral spectrin cytoskeleton and Ajuba, are dispensable for the R8 cell fate choice. Surprisingly, Crumbs promotes the Rhodopsin 5 cell fate, which is driven by Yorkie, rather than the Rhodopsin 6 cell fate, which is driven by Warts and the Hippo pathway, which contrasts with its impact on Hippo activity in organ growth. Furthermore, neither the apical spectrin cytoskeleton nor Crumbs appear to regulate the Hippo pathway through mechanisms that have been observed in growing organs. Together, these results show that only a subset of Hippo pathway proteins regulate the R8 binary cell fate decision and that aspects of Hippo signalling differ between growing organs and post-mitotic R8 cells.
Hippo 通路是调控器官生长和细胞命运的重要调节因子。在果蝇眼的 R8 光感受器细胞中,Hippo 通路控制着两种亚型细胞命运的选择,这两种亚型细胞分别表达对蓝光敏感的 Rhodopsin 5(Hippo 非活性 R8 亚型)或对绿光敏感的 Rhodopsin 6(Hippo 活性 R8 亚型)。Hippo 信号转导的机制及其介导的蛋白在器官生长和 R8 细胞命运选择中的保守程度目前尚不清楚。在这里,我们确定了 Crumbs 和顶端 spectrin 细胞骨架作为 R8 细胞命运的调节因子。相比之下,其他影响 Hippo 依赖性器官生长的蛋白质,如基底侧 spectrin 细胞骨架和 Ajuba,则对 R8 细胞命运选择是可有可无的。令人惊讶的是,Crums 促进了由 Yorkie 驱动的 Rhodopsin 5 细胞命运,而不是由 Warts 和 Hippo 通路驱动的 Rhodopsin 6 细胞命运,这与它对 Hippo 活性在器官生长中的影响形成了鲜明对比。此外,顶端 spectrin 细胞骨架和 Crumbs 似乎都没有通过在生长器官中观察到的机制来调节 Hippo 通路。综上所述,这些结果表明,只有 Hippo 通路蛋白的一部分调节 R8 二态细胞命运决定,并且 Hippo 信号通路在生长器官和有丝分裂后 R8 细胞之间存在差异。