TY  - JOUR
AU  - Vinopal, Stanislav
AU  - Dupraz, Sebastian
AU  - Alfadil, Eissa
AU  - Pietralla, Thorben
AU  - Bendre, Shweta
AU  - Stiess, Michael
AU  - Falk, Sven
AU  - Camargo Ortega, Germán
AU  - Maghelli, Nicola
AU  - Tolić, Iva M
AU  - Smejkal, Jiří
AU  - Götz, Magdalena
AU  - Bradke, Frank
TI  - Centrosomal microtubule nucleation regulates radial migration of projection neurons independently of polarization in the developing brain.
JO  - Neuron
VL  - 111
IS  - 8
SN  - 0896-6273
CY  - New York, NY
PB  - Elsevier
M1  - DZNE-2023-00489
SP  - 1241 - 1263.e16
PY  - 2023
AB  - 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.
KW  - Humans
KW  - Tubulin: metabolism
KW  - Neurons: physiology
KW  - Axons: metabolism
KW  - Microtubules: metabolism
KW  - Centrosome
KW  - Brain: metabolism
KW  - axon formation (Other)
KW  - centrosome (Other)
KW  - microtubule (Other)
KW  - neuronal polarity (Other)
KW  - radial migration (Other)
KW  - Tubulin (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:36796357
DO  - DOI:10.1016/j.neuron.2023.01.020
UR  - https://pub.dzne.de/record/257692
ER  -