Tavares Lígia, Correia Andreia, Santos Marília A, Relvas João B, Pereira Paulo S
i3S -Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
PLoS Genet. 2017 Mar 7;13(3):e1006647. doi: 10.1371/journal.pgen.1006647. eCollection 2017 Mar.
In the nervous system, glial cells provide crucial insulation and trophic support to neurons and are important for neuronal survival. In reaction to a wide variety of insults, glial cells respond with changes in cell morphology and metabolism to allow repair. Additionally, these cells can acquire migratory and proliferative potential. In particular, after axonal damage or pruning the clearance of axonal debris by glial cells is key for a healthy nervous system. Thus, bidirectional neuron-glial interactions are crucial in development, but little is known about the cellular sensors and signalling pathways involved. In here, we show that decreased cellular fitness in retinal progenitors caused by reduced Drosophila Myc expression triggers non cell-autonomous activation of retinal glia proliferation and overmigration. Glia migration occurs beyond its normal limit near the boundary between differentiated photoreceptors and precursor cells, extending into the progenitor domain. This overmigration is stimulated by JNK activation (and the function of its target Mmp1), while proliferative responses are mediated by Dpp/TGF-β signalling activation.
在神经系统中,神经胶质细胞为神经元提供关键的绝缘和营养支持,对神经元的存活至关重要。在对多种损伤做出反应时,神经胶质细胞会通过细胞形态和代谢的变化做出反应以实现修复。此外,这些细胞能够获得迁移和增殖潜能。特别是在轴突损伤或修剪后,神经胶质细胞清除轴突碎片对于健康的神经系统至关重要。因此,双向的神经元 - 神经胶质细胞相互作用在发育过程中至关重要,但对于其中涉及的细胞传感器和信号通路却知之甚少。在此,我们表明,果蝇Myc表达降低导致视网膜祖细胞的细胞适应性下降,从而引发视网膜神经胶质细胞增殖和过度迁移的非细胞自主性激活。神经胶质细胞迁移超出其在分化的光感受器和前体细胞之间边界附近的正常界限,延伸到祖细胞区域。这种过度迁移受到JNK激活(及其靶标Mmp1的功能)的刺激,而增殖反应则由Dpp/TGF-β信号激活介导。