Centrosomal microtubule nucleation regulates radial migration of projection neurons independently of polarization in the developing brain

Vinopal S, Dupraz S, Alfadil E, Pietralla T, Bendre S, Stiess M, Falk S, Ortega GC, Maghelli N, Tolic IM, Smejkal J, Goetz M, Bradke F (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Neuron Elsevier (Cell Press)

Book Volume: 111

Pages Range: 1241-+

Journal Issue: 8

DOI: 10.1016/j.neuron.2023.01.020

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 centro-somal microtubule nucleation abrogated radial migration without affecting axon formation. Tightly regu-lated 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 g-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 g-tubulin.

Authors with CRIS profile

Sven Falk Lehrstuhl für Biochemie und Pathobiochemie

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Related research project(s)

E032: Identifying molecular nexuses in microtubule-associated neurodevelopmental diseases July 1, 2023 - Dec. 31, 2025

Involved external institutions

Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) DE Germany (DE) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE) Max-Planck-Institut für molekulare Zellbiologie und Genetik / Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) DE Germany (DE) Jan Evangelista Purkyně University in Ústí nad Labem / Univerzita Jana Evangelisty Purkyně v Ústí nad Labem (UJEP) CZ Czech Republic (CZ) Ludwig-Maximilians-Universität (LMU) DE Germany (DE)

How to cite

APA:

Vinopal, S., Dupraz, S., Alfadil, E., Pietralla, T., Bendre, S., Stiess, M.,... Bradke, F. (2023). Centrosomal microtubule nucleation regulates radial migration of projection neurons independently of polarization in the developing brain. Neuron, 111(8), 1241-+. https://doi.org/10.1016/j.neuron.2023.01.020

MLA:

Vinopal, Stanislav, et al. "Centrosomal microtubule nucleation regulates radial migration of projection neurons independently of polarization in the developing brain." Neuron 111.8 (2023): 1241-+.

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