Dynamic changes in ultrastructure of the primary cilium in migrating neuroblasts in the postnatal brain

概要

New neurons, referred to as neuroblasts, are continuously generated in the ventricular-subventricular zone of the brain throughout an animal’s life (Obernier and Alvarez-Buylla, 2019). These neuroblasts are characterized by their unique potential for proliferation (Ikeda et al., 2010; Ponti et al., 2013), formation of chain- like cell aggregates (Lois et al., 1996; Sawamoto et al., 2006) , and long-distance and high-speed migration through the rostral migratory stream (RMS) toward the olfactory bulb (OB) (Luskin, 1993; Lois and Alvarez-Buylla, 1994; Lois et al., 1996), where they decelerate and differentiate into mature interneurons (Luskin, 1993; Lois and Alvarez-Buylla, 1994; Sawada et al., 2018). The dynamic changes of ultrastructural features in postnatal-born neuroblasts during migration are not yet fully understood. Here we report the presence of a primary cilium, and its ultrastructural morphology and spatiotemporal dynamics, in migrating neuroblasts in the postnatal RMS and OB. The primary cilium was observed in migrating neuroblasts in the postnatal RMS and OB in male and female mice and zebrafish, and a male rhesus monkey. Inhibition of intraflagellar transport molecules in migrating neuroblasts impaired their ciliogenesis and rostral migration toward the OB. Serial section transmission electron microscopy revealed that each migrating neuroblast possesses either a pair of centrioles, or a basal body with an immature or mature primary cilium. Using immunohistochemistry, live imaging, and serial block-face scanning electron microscopy, we demonstrate that the localization and orientation of the primary cilium are altered depending on the mitotic state, saltatory migration, and deceleration of neuroblasts. Together, our results highlight a close mutual relationship between spatiotemporal regulation of the primary cilium and efficient chain migration of neuroblasts in the postnatal brain.