TY  - JOUR
AU  - Da Silva Santos, Telma
AU  - Schaffran, Barbara
AU  - Broguière, Nicolas
AU  - Meyn, Liane
AU  - Zenobi-Wong, Marcy
AU  - Bradke, Frank
TI  - Axon Growth of CNS Neurons in Three Dimensions Is Amoeboid and Independent of Adhesions
JO  - Cell reports
VL  - 32
IS  - 3
SN  - 2211-1247
CY  - [New York, NY]
PB  - Elsevier
M1  - DZNE-2020-01278
SP  - 107907
PY  - 2020
AB  - SummaryDuring 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.
KW  - Actins: metabolism
KW  - Actomyosin: metabolism
KW  - Animals
KW  - Axons: metabolism
KW  - Cell Adhesion
KW  - Cell Polarity
KW  - Central Nervous System: metabolism
KW  - Collagen: metabolism
KW  - Fibroblasts: metabolism
KW  - Growth Cones: metabolism
KW  - Hippocampus: embryology
KW  - Mice, Inbred C57BL
KW  - Microtubules: metabolism
KW  - Neuronal Outgrowth
KW  - Polymerization
LB  - PUB:(DE-HGF)16
C6  - pmid:32698008
DO  - DOI:10.1016/j.celrep.2020.107907
UR  - https://pub.dzne.de/record/153281
ER  -