Journal Article

DZNE-2020-07935

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png RhoA Controls Axon Extension Independent of Specification in the Developing Brain.

Dupraz, S.DZNE* ; Hilton, B. J.DZNE* ; Husch, A.DZNE* ; Da Silva Santos, T.DZNE* ; Coles, C. H.DZNE* ; Stern, S.DZNE* ; Brakebusch, C. ; Bradke, F. (First author)DZNE*

2019
Current Biology Ltd. London

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Please use a persistent id in citations: doi:10.1016/j.cub.2019.09.040

Abstract: 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.

Keyword(s): Actin Cytoskeleton: metabolism (MeSH) ; Actins: metabolism (MeSH) ; Animals (MeSH) ; Axons: metabolism (MeSH) ; Axons: physiology (MeSH) ; Brain: embryology (MeSH) ; Brain: metabolism (MeSH) ; Cell Polarity: physiology (MeSH) ; Female (MeSH) ; Gain of Function Mutation: genetics (MeSH) ; Growth Cones: metabolism (MeSH) ; Loss of Function Mutation: genetics (MeSH) ; Male (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Transgenic (MeSH) ; Microtubules: metabolism (MeSH) ; Myosin Type II: metabolism (MeSH) ; Neurogenesis: physiology (MeSH) ; Neurons: metabolism (MeSH) ; rhoA GTP-Binding Protein: genetics (MeSH) ; rhoA GTP-Binding Protein: metabolism (MeSH) ; rhoA GTP-Binding Protein: physiology (MeSH)

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Contributing Institute(s):

1. Axon Growth and Regeneration (AG Bradke)

Research Program(s):

1. 341 - Molecular Signaling (POF3-341) (POF3-341)

Appears in the scientific report 2019

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Database coverage:
; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 10 ; JCR ; Nationallizenz ; SCOPUS ; Web of Science Core Collection ; Zoological Record

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