Macrophages Break Interneuromast Cell Quiescence by Intervening in the Inhibition of Schwann Cells in the Zebrafish Lateral Line

In the zebrafish lateral line system, interneuromast cells (INCs) between neuromasts are kept quiescent by underlying Schwann cells (SWCs). Upon severe injuries that cause the complete loss of an entire neuromast, INCs can occasionally differentiate into neuromasts but how they escape from the inhibition by SWCs is still unclear. Using a genetic/chemical method to ablate a neuromast precisely, we found that a small portion of larvae can regenerate a new neuromast. However, the residual regeneration capacity was hindered by inhibiting macrophages. Using in toto imaging, we further discovered heterogeneities in macrophage behavior and distribution along the lateral line. We witnessed the crawling of macrophages between the injured lateral line and SWCs during regeneration and between the second primordium and the first mature lateral line during development. It implies that macrophages may physically alleviate the nerve inhibition to break the dormancy of INCs during regeneration and development in the zebrafish lateral line.