Mode and Tempo of Tangential Cell Migration in the Cerebellar External Granular Layer

Abstract

After their final mitosis, cerebellar granule cells remain in the external granular layer (EGL) for 20-48 hr before initiating their radial migration across the molecular layer (ML), but the significance of this latent period is not well understood. In the present study, we used a confocal microscope to examine morphogenetic changes and behavior of postmitotic granule cells restricted to the EGL in slice preparations of the postnatal mouse cerebellum. We found that, coincident with the extension of two uneven horizontal processes oriented parallel to the longitudinal axis of the folium, postmitotic granule cells start to migrate tangentially in the direction of the larger process. Interestingly, their morphology and the speed of cell movement change systematically with their position within the EGL. The rate of tangential cell movement is fastest (ϳ14.8 m/hr) in the middle of the EGL, when cells have two short horizontal processes. As granule cells elongate their somata and extend longer horizontal processes at the bottom of the EGL, they move at a reduced rate (ϳ12.6 m/hr). At the interface of the EGL and ML where cells migrate tangentially at the slowest rate (ϳ4.1 m/hr), their somata round and then begin to extend couples of the descending processes into the ML. After the stationary period, granule cells abruptly extend a single vertical process and initiate the transition from tangential to radial migration, reshaping their rounded somata into a vertically elongated spindle. These observations suggest that tangential migration of granule cells within the EGL may provide the developmental mechanisms for their appropriate allocation across parasagittal compartments of the expanding cerebellar cortex.

Long-term in vivo single-cell tracking reveals the switch of migration patterns in adult-born juxtaglomerular cells of the mouse olfactory bulb

“…In previous in vitro studies, the intermittent stops during the migration of individual cells were rather brief, giving an impression of a continuous movement [11,15,34,35], but many JGNs analyzed here stopped for very long time periods (from 12 h to a few days) before resuming the movement. Continuous imaging of the cells at high temporal resolution, i.e., every 15 min, revealed that cells were migrating at median speeds of 0.4-0.8 µm/min, or 24-48 µm/h, which are comparable to the values obtained in organotypic slices from perinatal mice for cells detaching from the RMS and starting radial migration into the bulb [12], or for SVZ neuroblasts migrating in exploratory/intermediate manner in acute OB slices from juvenile/adult mice [15].…”

Tangential migration of neuronal precursors of glutamatergic neurons in the adult mammalian brain

“…It may be that radial and tangential migration modes are not specific to neurons releasing a specific neurotransmitter. Indeed, in the cerebellum, inhibitory principal Purkinje neurons exhibit radial migration, whereas excitatory modulatory granule neurons migrate tangentially as well as radially (23). A very small number of glutamatergic modulatory interneurons are also generated in the adult SVZ and migrate tangentially to the olfactory bulb (24).…”

Initiating and Growing an Axon

“…In other neuronal subpopulations undergoing long-range migration, neuronal morphogenesis undergoes extensive stereotypical changes, leading to polarized outgrowth of their axon and dendrites. This is the case for cerebellar granule neurons (CGN) as well as cortical and hippocampal pyramidal neurons (PN), two of the best-studied models of neuronal polarization (Rakic 1971;Rakic 1972;Shoukimas and Hinds 1978;Gao and Hatten 1993;Komuro et al 2001;Hatanaka and Murakami 2002;Noctor et al 2004). Both CGN and PN acquire their axon -dendrite polarity from the polarized emergence during migration of their trailing and leading processes, respectively (Fig.…”