1. Centrosomal microtubule nucleation regulates radial migration of projection neurons independently of polarization in the developing brain.
- Author
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Vinopal, Stanislav, Dupraz, Sebastian, Alfadil, Eissa, Pietralla, Thorben, Bendre, Shweta, Stiess, Michael, Falk, Sven, Camargo Ortega, Germán, Maghelli, Nicola, Tolić, Iva M., Smejkal, Jiří, Götz, Magdalena, and Bradke, Frank
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MICROTUBULES , *NEURONS , *NUCLEATION , *THREE-dimensional imaging , *NEURAL circuitry - Abstract
Cortical projection neurons polarize and form an axon while migrating radially. Even though these dynamic processes are closely interwoven, they are regulated separately—the neurons terminate their migration when reaching their destination, the cortical plate, but continue to grow their axons. Here, we show that in rodents, the centrosome distinguishes these processes. Newly developed molecular tools modulating centrosomal microtubule nucleation combined with in vivo imaging uncovered that dysregulation of centrosomal microtubule nucleation abrogated radial migration without affecting axon formation. Tightly regulated centrosomal microtubule nucleation was required for periodic formation of the cytoplasmic dilation at the leading process, which is essential for radial migration. The microtubule nucleating factor γ-tubulin decreased at neuronal centrosomes during the migratory phase. As distinct microtubule networks drive neuronal polarization and radial migration, this provides insight into how neuronal migratory defects occur without largely affecting axonal tracts in human developmental cortical dysgeneses, caused by mutations in γ-tubulin. [Display omitted] • Neurons polarize independently of centrosomal microtubule nucleation (CMN) • The centrosome loses γ-tubulin as neurons enter the cortical plate • CMN changes correlate with the cytoplasmic dilation in radially migrating neurons • CMN regulates radial migration independently of axon formation in the developing brain Combining a novel expression system with live in vivo imaging, three-dimensional two-photon imaging, and centrosomal ablation, Vinopal and Dupraz et al. demonstrate that neurons need centrosomal microtubule nucleation for their radial migration but not axon formation. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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