Neural Crest Cells Phagocytose Debris in the Developing Central Nervous System

During early neurogenesis, almost half of the cells in the central nervous system (CNS) and the peripheral nervous system (PNS) undergo apoptosis, which generates cellular debris. This debris must be cleared to prevent interference with normal development. In adults, debris in the CNS, including the brain and neural tube, is cleared by myeloid-derived microglia. However, microglia develop relatively late and do not colonize the spinal cord when massive cell death occurs. Therefore, it is currently unknown how cellular debris is cleared in the spinal cord during early neurogenesis. Recently, our lab discovered that neural crest cells (NCCs), which appear at the dorsal neural tube during neurogenesis and are some of the most highly migratory cells in the body, engulf and phagocytose cellular debris in the PNS during neurogenesis. Interestingly, although they are a PNS lineage, we observed NCCs ectopically entering the CNS through the motor exit point (MEP) for unknown reasons. Here, using selective ablation of radial glia and time-lapse confocal microscopy in zebrafish (Danio rerio), we show that NCCs can migrate through the MEP into the spinal cord to clear CNS cellular debris at early developmental stages. Their recruitment into the CNS and rate of division increases during events of massive cell death, and their ability to enter the CNS significantly decreases after 40 hours post fertilization (hpf). These results provide a mechanism for CNS debris clearance during early embryogenesis in the absence of microglia. This novel function of NCCs may have implications for debris clearance in neurodegenerative diseases.