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000257692 1001_ $$0P:(DE-2719)2810898$$aVinopal, Stanislav$$b0$$eFirst author$$udzne
000257692 245__ $$aCentrosomal microtubule nucleation regulates radial migration of projection neurons independently of polarization in the developing brain.
000257692 260__ $$aNew York, NY$$bElsevier$$c2023
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000257692 520__ $$aCortical 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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000257692 650_7 $$2Other$$aaxon formation
000257692 650_7 $$2Other$$acentrosome
000257692 650_7 $$2Other$$amicrotubule
000257692 650_7 $$2Other$$aneuronal polarity
000257692 650_7 $$2Other$$aradial migration
000257692 650_7 $$2NLM Chemicals$$aTubulin
000257692 650_2 $$2MeSH$$aHumans
000257692 650_2 $$2MeSH$$aTubulin: metabolism
000257692 650_2 $$2MeSH$$aNeurons: physiology
000257692 650_2 $$2MeSH$$aAxons: metabolism
000257692 650_2 $$2MeSH$$aMicrotubules: metabolism
000257692 650_2 $$2MeSH$$aCentrosome
000257692 650_2 $$2MeSH$$aBrain: metabolism
000257692 7001_ $$0P:(DE-2719)2810386$$aDupraz, Sebastian$$b1$$udzne
000257692 7001_ $$0P:(DE-2719)9000994$$aAlfadil, Eissa$$b2$$udzne
000257692 7001_ $$0P:(DE-2719)2814321$$aPietralla, Thorben$$b3$$udzne
000257692 7001_ $$0P:(DE-2719)2812523$$aBendre, Shweta$$b4$$udzne
000257692 7001_ $$0P:(DE-2719)2810316$$aStiess, Michael$$b5$$udzne
000257692 7001_ $$aFalk, Sven$$b6
000257692 7001_ $$aCamargo Ortega, Germán$$b7
000257692 7001_ $$aMaghelli, Nicola$$b8
000257692 7001_ $$aTolić, Iva M$$b9
000257692 7001_ $$aSmejkal, Jiří$$b10
000257692 7001_ $$aGötz, Magdalena$$b11
000257692 7001_ $$0P:(DE-2719)2810270$$aBradke, Frank$$b12$$eLast author$$udzne
000257692 773__ $$0PERI:(DE-600)2001944-0$$a10.1016/j.neuron.2023.01.020$$gVol. 111, no. 8, p. 1241 - 1263.e16$$n8$$p1241 - 1263.e16$$tNeuron$$v111$$x0896-6273$$y2023
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