Abstract
The cerebellum arguably constitutes one of the best characterized central nervous circuits, and its structure, cellular function, and histogenesis have been described in exceptional quantitative detail. A notable exception to this is the development of its inhibitory interneurons, and in particular the extensive migrations of future basket and stellate cells. Here, we used acute slices from 8-day-old mice to assess the migration of Pax2-EGFP-tagged precursors of these cells en route to the molecular layer during their transit through the nascent cerebellar cortex. We document that movement of these cells is highly directed. Their speed and directional persistence are larger in the nascent granule cell layer than in the molecular layer. And they migrate periodically, with periods of effective, directed translocation separated by bouts of rather local movement. Finally, we document that the arrangement of these cells in the adult molecular layer is characterized by clustering. These data are discussed with a focus on potential generative mechanisms for the developmental pattern observed.
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Acknowledgments
This work was supported by grants of the German Research Foundation [SPP1757: STE 552/5 to C.S., JA 942-1/2 to RJ] and the European Union [ERA-NET NEURON: BrIE to C.S.].
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Supplementary Movie 1
This movie shows translocation of several cells through the nascent cerebellar cortex. The border of the white matter is close to the right hand margin of the scene, that of the EGL close to the left hand margin. In the initial still image, the approximate position of the Purkinje cell layer is indicated by white dots. The three yellow arrowheads in this still mark Pax2 cells that migrate extensively. One of them is actually hidden underneath a large, immobile (Golgi) cell at the start of the scene. The red arrow indicates a group of Pax2 cells at the fringe of the white matter, one of which effectively migrates into the granule cell layer. The position of the perikarya of these cells is again marked with arrows in the still at the end of the scene. Next, cell tracks are shown, and the translocation of the cells’ centers of gravity defining these paths. Not that the speed of translocation varies considerably over the 4 h period shown, with phases of effective translocation interspersed with phases of low mobility. (MP4 10088 kb)
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Wefers, A.K., Haberlandt, C., Surchev, L. et al. Migration of Interneuron Precursors in the Nascent Cerebellar Cortex. Cerebellum 17, 62–71 (2018). https://doi.org/10.1007/s12311-017-0900-7
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DOI: https://doi.org/10.1007/s12311-017-0900-7