Poulton John S, Cuningham John C, Peifer Mark
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Dev Cell. 2014 Sep 29;30(6):731-45. doi: 10.1016/j.devcel.2014.08.007. Epub 2014 Sep 18.
Mitotic spindles are critical for accurate chromosome segregation. Centrosomes, the primary microtubule nucleating centers of animal cells, play key roles in forming and orienting mitotic spindles. However, the survival of Drosophila without centrosomes suggested they are dispensable in somatic cells, challenging the canonical view. We used fly wing disc epithelia as a model to resolve these conflicting hypotheses, revealing that centrosomes play vital roles in spindle assembly, function, and orientation. Many acentrosomal cells exhibit prolonged spindle assembly, chromosome missegregation, DNA damage, misoriented divisions, and eventual apoptosis. We found that multiple mechanisms buffer the effects of centrosome loss, including alternative microtubule nucleation pathways and the spindle assembly checkpoint. Apoptosis of acentrosomal cells is mediated by JNK signaling, which also drives compensatory proliferation to maintain tissue integrity and viability. These data reveal the importance of centrosomes in fly epithelia and demonstrate the robust compensatory mechanisms at the cellular and organismal level.
有丝分裂纺锤体对于准确的染色体分离至关重要。中心体是动物细胞主要的微管成核中心,在形成和定向有丝分裂纺锤体中起关键作用。然而,果蝇在没有中心体的情况下仍能存活,这表明它们在体细胞中是可有可无的,这对传统观点提出了挑战。我们以果蝇翅芽上皮为模型来解决这些相互矛盾的假说,结果表明中心体在纺锤体组装、功能和定向中起着至关重要的作用。许多无中心体细胞表现出纺锤体组装延长、染色体错分离、DNA损伤、分裂方向错误以及最终的细胞凋亡。我们发现多种机制缓冲了中心体缺失的影响,包括替代性微管成核途径和纺锤体组装检查点。无中心体细胞的凋亡由JNK信号介导,该信号还驱动代偿性增殖以维持组织完整性和活力。这些数据揭示了中心体在果蝇上皮中的重要性,并证明了细胞和机体水平上强大的代偿机制。