Polarity, Division and Morphogenesis Team, Institut Curie, CNRS UMR 3215, INSERM U934, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
Development. 2013 Jul;140(13):2657-68. doi: 10.1242/dev.087338. Epub 2013 May 29.
Asymmetric cell division generates cell fate diversity during development and adult life. Recent findings have demonstrated that during stem cell divisions, the movement of centrosomes is asymmetric in prophase and that such asymmetry participates in mitotic spindle orientation and cell polarization. Here, we have investigated the dynamics of centrosomes during Drosophila sensory organ precursor asymmetric divisions and find that centrosome movements are asymmetric during cytokinesis. We demonstrate that centrosome movements are controlled by the cell fate determinant Numb, which does not act via its classical effectors, Sanpodo and α-Adaptin, but via the Collapsin Response Mediator Protein (CRMP). Furthermore, we find that CRMP is necessary for efficient Notch signalling and that it regulates the duration of the pericentriolar accumulation of Rab11-positive endosomes, through which the Notch ligand, Delta is recycled. Our work characterizes an additional mode of asymmetric centrosome movement during asymmetric divisions and suggests a model whereby the asymmetry in centrosome movements participates in differential Notch activation to regulate cell fate specification.
不对称细胞分裂在发育和成年期产生细胞命运多样性。最近的研究结果表明,在干细胞分裂过程中,中心体在前期的运动是不对称的,这种不对称参与了有丝分裂纺锤体的定向和细胞极化。在这里,我们研究了果蝇感觉器官前体细胞不对称分裂过程中中心体的动力学,发现中心体在胞质分裂过程中的运动是不对称的。我们证明,中心体的运动受细胞命运决定因子 Numb 的控制,Numb 不是通过其经典效应物 Sanpodo 和 α-Adaptin 起作用,而是通过 Collapsin Response Mediator Protein (CRMP) 起作用。此外,我们发现 CRMP 对于 Notch 信号的有效传递是必需的,并且它通过 Rab11 阳性内体的中心粒周围聚集的持续时间来调节, Notch 配体 Delta 通过该内体被回收。我们的工作描述了不对称分裂过程中另一种不对称中心体运动的模式,并提出了一种模型,即中心体运动的不对称性参与了 Notch 激活的差异,以调节细胞命运的特化。