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Vinopal, S.* ; Dupraz, S.* ; Alfadil, E.* ; Pietralla, T.* ; Bendre, S.* ; Stiess, M.* ; Falk, S. ; Camargo Ortega, G. ; Maghelli, N.* ; Tolić, I.M.* ; Smejkal, J.* ; Götz, M. ; Bradke, F.*

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

Neuron 111, 1241-1263.e16 (2023)

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Open Access Green as soon as Postprint is submitted to ZB.

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Axon Formation ; Centrosome ; Microtubule ; Neuronal Polarity ; Radial Migration; Gamma-tubulin; Axon Regeneration; Golgi-apparatus; Cell Polarity; Organization; Cdk5rap2; Dynamics; Pathway; Lis1; Recruitment

ISSN (print) / ISBN 0896-6273

e-ISSN 1097-4199

Journal Neuron

Quellenangaben Volume: 111, Issue: 8, Pages: 1241-1263.e16

Publisher Cell Press

Publishing Place Cambridge, Mass.

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Stem Cell Research (ISF)

Grants Roger de Spoelberch Prize
ERANET AXON REPAIR
DFG
WFL
IRP
ERC
ERANET RATER SCI