RhoA Controls Axon Extension Independent of Specification in the Developing Brain

Sebastian Dupraz, Brett J Hilton, Andreas Husch, Telma E Santos, Charlotte H Coles, Sina Stern, Cord Brakebusch, Frank Bradke

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    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.

    OriginalsprogEngelsk
    TidsskriftCurrent biology : CB
    Vol/bind29
    Udgave nummer22
    Sider (fra-til)3874-3886
    Antal sider22
    ISSN0960-9822
    DOI
    StatusUdgivet - 18 nov. 2019

    Bibliografisk note

    Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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