Saade Murielle, Gonzalez-Gobartt Elena, Escalona Rene, Usieto Susana, Martí Elisa
Instituto de Biología Molecular de Barcelona, CSIC, ParcCientífic de Barcelona, C/Baldiri i Reixac 20, Barcelona 08028, Spain.
Nat Cell Biol. 2017 Apr 27;19(5):493-503. doi: 10.1038/ncb3512.
Tight control of the balance between self-expanding symmetric and self-renewing asymmetric neural progenitor divisions is crucial to regulate the number of cells in the developing central nervous system. We recently demonstrated that Sonic hedgehog (Shh) signalling is required for the expansion of motor neuron progenitors by maintaining symmetric divisions. Here we show that activation of Shh/Gli signalling in dividing neuroepithelial cells controls the symmetric recruitment of PKA to the centrosomes that nucleate the mitotic spindle, maintaining symmetric proliferative divisions. Notably, Shh signalling upregulates the expression of pericentrin, which is required to dock PKA to the centrosomes, which in turn exerts a positive feedback onto Shh signalling. Thus, by controlling centrosomal protein assembly, we propose that Shh signalling overcomes the intrinsic asymmetry at the centrosome during neuroepithelial cell division, thereby promoting self-expanding symmetric divisions and the expansion of the progenitor pool.
严格控制自我扩张的对称型与自我更新的不对称型神经祖细胞分裂之间的平衡,对于调节发育中的中枢神经系统中的细胞数量至关重要。我们最近证明, Sonic hedgehog(Shh)信号传导通过维持对称分裂对于运动神经元祖细胞的扩增是必需的。在这里,我们表明,在分裂的神经上皮细胞中激活Shh/Gli信号传导可控制PKA向有丝分裂纺锤体成核的中心体的对称募集,维持对称增殖分裂。值得注意的是,Shh信号传导上调了中心粒外周蛋白的表达,这是将PKA对接至中心体所必需的,而中心体又对Shh信号传导产生正反馈。因此,通过控制中心体蛋白组装,我们提出Shh信号传导在神经上皮细胞分裂过程中克服了中心体的内在不对称性,从而促进自我扩张的对称分裂和祖细胞池的扩增。