Migratory Neural Crest Cells Phagocytose Cellular Debris in the Developing Nervous System

Abstract

During neural tube closure and subsequent spinal cord development, a vast number of cells undergo programmed cell death 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 early development remains largely unknown. Using live imaging in zebrafish, we demonstrate that multipotent neural crest cells (NCC) respond rapidly to dying cells and phagocytose cellular debris around the neural tube. Furthermore, migratory NCCs have the ability to enter the CNS through motor exit point transition zones and clear debris in the spinal cord. Surprisingly, NCC phagocytosis mechanistically resembles macrophage phagocytosis and their recruitment towards cellular debris is mediated by interleukin-1β signaling. Taken together, our results reveal an unexpected role of NCCs in phagocytosis of debris in the developing nervous system before the presence of professional phagocytes.