Department of Biology, University of Virginia, Charlottesville, VA 22904, USA.
Department of Biology, University of Virginia, Charlottesville, VA 22904, USA.
Cell. 2019 Sep 19;179(1):74-89.e10. doi: 10.1016/j.cell.2019.08.001. Epub 2019 Sep 5.
During neural tube closure and spinal cord development, many cells die in both the central and peripheral nervous systems (CNS and PNS, respectively). However, myeloid-derived professional phagocytes have not yet colonized the trunk region during early neurogenesis. How apoptotic cells are removed from this region during these stages remains largely unknown. Using live imaging in zebrafish, we demonstrate that neural crest cells (NCCs) respond rapidly to dying cells and phagocytose cellular debris around the neural tube. Additionally, NCCs have the ability to enter the CNS through motor exit point transition zones and clear debris in the spinal cord. Surprisingly, NCCs phagocytosis mechanistically resembles macrophage phagocytosis and their recruitment toward cellular debris is mediated by interleukin-1β. Taken together, our results reveal a role for NCCs in phagocytosis of debris in the developing nervous system before the presence of professional phagocytes.
在神经管闭合和脊髓发育过程中,中枢神经系统(CNS)和周围神经系统(PNS)中的许多细胞都会死亡。然而,在早期神经发生过程中,髓系来源的专业吞噬细胞尚未在躯干区域定植。在这些阶段,细胞凋亡是如何从该区域清除的,目前还知之甚少。通过在斑马鱼中的活体成像,我们证明神经嵴细胞(NCCs)能够快速响应凋亡细胞,并吞噬神经管周围的细胞碎片。此外,NCCs 能够通过运动神经出口过渡区进入 CNS,并清除脊髓中的碎片。令人惊讶的是,NCCs 的吞噬作用在机制上类似于巨噬细胞吞噬作用,白细胞介素-1β介导了它们向细胞碎片的募集。总之,我们的研究结果揭示了 NCCs 在专业吞噬细胞出现之前,在发育中的神经系统中吞噬碎片的作用。