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000153281 0247_ $$2doi$$a10.1016/j.celrep.2020.107907
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000153281 037__ $$aDZNE-2020-01278
000153281 041__ $$aEnglish
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000153281 1001_ $$0P:(DE-2719)2810952$$aDa Silva Santos, Telma$$b0$$eFirst author$$udzne
000153281 245__ $$aAxon Growth of CNS Neurons in Three Dimensions Is Amoeboid and Independent of Adhesions
000153281 260__ $$a[New York, NY]$$bElsevier$$c2020
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000153281 520__ $$aSummaryDuring development of the central nervous system (CNS), neurons polarize and rapidly extend their axons to assemble neuronal circuits. The growth cone leads the axon to its target and drives axon growth. Here, we explored the mechanisms underlying axon growth in three dimensions. Live in situ imaging and super-resolution microscopy combined with pharmacological and molecular manipulations as well as biophysical force measurements revealed that growth cones extend CNS axons independent of pulling forces on their substrates and without the need for adhesions in three-dimensional (3D) environments. In 3D, microtubules grow unrestrained from the actomyosin cytoskeleton into the growth cone leading edge to enable rapid axon extension. Axons extend and polarize even in adhesion-inert matrices. Thus, CNS neurons use amoeboid mechanisms to drive axon growth. Together with our understanding that adult CNS axons regenerate by reactivating developmental processes, our findings illuminate how cytoskeletal manipulations enable axon regeneration in the adult CNS.
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000153281 650_2 $$2MeSH$$aActins: metabolism
000153281 650_2 $$2MeSH$$aActomyosin: metabolism
000153281 650_2 $$2MeSH$$aAnimals
000153281 650_2 $$2MeSH$$aAxons: metabolism
000153281 650_2 $$2MeSH$$aCell Adhesion
000153281 650_2 $$2MeSH$$aCell Polarity
000153281 650_2 $$2MeSH$$aCentral Nervous System: metabolism
000153281 650_2 $$2MeSH$$aCollagen: metabolism
000153281 650_2 $$2MeSH$$aFibroblasts: metabolism
000153281 650_2 $$2MeSH$$aGrowth Cones: metabolism
000153281 650_2 $$2MeSH$$aHippocampus: embryology
000153281 650_2 $$2MeSH$$aMice, Inbred C57BL
000153281 650_2 $$2MeSH$$aMicrotubules: metabolism
000153281 650_2 $$2MeSH$$aNeuronal Outgrowth
000153281 650_2 $$2MeSH$$aPolymerization
000153281 7001_ $$0P:(DE-2719)2811123$$aSchaffran, Barbara$$b1$$udzne
000153281 7001_ $$aBroguière, Nicolas$$b2
000153281 7001_ $$0P:(DE-2719)2810287$$aMeyn, Liane$$b3$$udzne
000153281 7001_ $$aZenobi-Wong, Marcy$$b4
000153281 7001_ $$0P:(DE-2719)2810270$$aBradke, Frank$$b5$$eLast author$$udzne
000153281 773__ $$0PERI:(DE-600)2649101-1$$a10.1016/j.celrep.2020.107907$$gVol. 32, no. 3, p. 107907 -$$n3$$p107907$$tCell reports$$v32$$x2211-1247$$y2020
000153281 8564_ $$uhttps://www.sciencedirect.com/science/article/pii/S2211124720308883
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