Centrosomal microtubule nucleation regulates radial migration of projection neurons independently of polarization in the developing brain
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
36796357
DOI
10.1016/j.neuron.2023.01.020
PII: S0896-6273(23)00070-3
Knihovny.cz E-resources
- Keywords
- axon formation, centrosome, microtubule, neuronal polarity, radial migration,
- MeSH
- Axons metabolism MeSH
- Centrosome MeSH
- Humans MeSH
- Microtubules metabolism MeSH
- Brain metabolism MeSH
- Neurons * physiology MeSH
- Tubulin * metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Tubulin * MeSH
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.
References provided by Crossref.org
Neuronal maturation and axon regeneration: unfixing circuitry to enable repair
