TY  - JOUR
AU  - Dupraz, Sebastian
AU  - Hilton, Brett J
AU  - Husch, Andreas
AU  - Da Silva Santos, Telma
AU  - Coles, Charlotte H
AU  - Stern, Sina
AU  - Brakebusch, Cord
AU  - Bradke, Frank
TI  - RhoA Controls Axon Extension Independent of Specification in the Developing Brain.
JO  - Current biology
VL  - 29
IS  - 22
SN  - 0960-9822
CY  - London
PB  - Current Biology Ltd.
M1  - DZNE-2020-07935
SP  - 3874-3886.e9
PY  - 2019
AB  - The specification of an axon and its subsequent outgrowth are key steps during neuronal polarization, a prerequisite to wire the brain. The Rho-guanosine triphosphatase (GTPase) RhoA is believed to be a central player in these processes. However, its physiological role has remained undefined. Here, genetic loss- and gain-of-function experiments combined with time-lapse microscopy, cell culture, and in vivo analysis show that RhoA is not involved in axon specification but confines the initiation of neuronal polarization and axon outgrowth during development. Biochemical analysis and super-resolution microscopy together with molecular and pharmacological manipulations reveal that RhoA restrains axon growth by activating myosin-II-mediated actin arc formation in the growth cone to prevent microtubules from protruding toward the leading edge. Through this mechanism, RhoA regulates the duration of axon growth and pause phases, thus controlling the tightly timed extension of developing axons. Thereby, this work unravels physiologically relevant players coordinating actin-microtubule interactions during axon growth.
KW  - Actin Cytoskeleton: metabolism
KW  - Actins: metabolism
KW  - Animals
KW  - Axons: metabolism
KW  - Axons: physiology
KW  - Brain: embryology
KW  - Brain: metabolism
KW  - Cell Polarity: physiology
KW  - Female
KW  - Gain of Function Mutation: genetics
KW  - Growth Cones: metabolism
KW  - Loss of Function Mutation: genetics
KW  - Male
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Mice, Transgenic
KW  - Microtubules: metabolism
KW  - Myosin Type II: metabolism
KW  - Neurogenesis: physiology
KW  - Neurons: metabolism
KW  - rhoA GTP-Binding Protein: genetics
KW  - rhoA GTP-Binding Protein: metabolism
KW  - rhoA GTP-Binding Protein: physiology
LB  - PUB:(DE-HGF)16
C6  - pmid:31679934
DO  - DOI:10.1016/j.cub.2019.09.040
UR  - https://pub.dzne.de/record/141611
ER  -