William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, UK.
Mol Neurobiol. 2009 Dec;40(3):195-215. doi: 10.1007/s12035-009-8081-0. Epub 2009 Aug 29.
The insulin-like growth factor receptor type 1 (IGF1R) signalling pathway is activated in the mammalian nervous system from early developmental stages. Its major effect on developing neural cells is to promote their growth and survival. This pathway can integrate its action with signalling pathways of growth and morphogenetic factors that induce cell fate specification and selective expansion of specified neural cell subsets. This suggests that during developmental and adult neurogenesis cellular responses to many signalling factors, including ligands of Notch, sonic hedgehog, fibroblast growth factor family members, ligands of the epidermal growth factor receptor, bone morphogenetic proteins and Wingless and Int-1, may be modified by co-activation of the IGF1R. Modulation of cell migration is another possible role that IGF1R activation may play in neurogenesis. Here, I briefly overview neurogenesis and discuss a role for IGF1R-mediated signalling in the developing and mature nervous system with emphasis on crosstalk between the signalling pathways of the IGF1R and other factors regulating neural cell development and migration. Studies on neural as well as on non-neural cells are highlighted because it may be interesting to test in neurogenic paradigms some of the models based on the information obtained in studies on non-neural cell types.
胰岛素样生长因子受体 1 型(IGF1R)信号通路在哺乳动物神经系统中从早期发育阶段就被激活。它对发育中的神经细胞的主要作用是促进其生长和存活。该途径可以将其作用与诱导细胞命运特化和特定神经细胞亚群选择性扩增的生长和形态发生因子的信号通路整合在一起。这表明,在发育和成年神经发生过程中,细胞对许多信号因子的反应,包括 Notch、sonic hedgehog、成纤维细胞生长因子家族成员、表皮生长因子受体配体、骨形态发生蛋白和 Wingless 和 Int-1 的配体,可能通过 IGF1R 的共激活而改变。细胞迁移的调节是 IGF1R 激活在神经发生中可能发挥的另一个作用。在这里,我简要概述神经发生,并讨论 IGF1R 介导的信号在发育和成熟神经系统中的作用,重点是 IGF1R 信号通路与其他调节神经细胞发育和迁移的因子之间的信号通路的串扰。突出了对神经细胞和非神经细胞的研究,因为在神经发生的范例中测试一些基于非神经细胞类型研究获得的模型可能会很有趣。