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The Journal of Neuroscience, March 1, 2002, 22(5):1794-1806

Growth Cone Pathfinding and Filopodial Dynamics Are Mediated Separately by Cdc42 Activation

Michael D. Kim¹, Peter Kolodziej², and Akira Chiba¹

¹ Department of Cell and Structural Biology, University of Illinois, Urbana, Illinois 61801, and ² Department of Cell and Developmental Biology, Center for Molecular Neuroscience, Vanderbilt University Medical Center, Nashville, Tennessee 37232

Although evidence exists that activation of the Rho family GTPase Cdc42 affects axonal development, its specific roles within a growth cone are not well delineated. To evaluate the model that Cdc42 activation regulates growth cone navigation by promoting filopodial activity, we adopted a live analysis strategy that uses transgenic Drosophila lines in which neurons coexpressed constitutively active Cdc42 (Cdc42^V12) and membrane-targeted green fluorescent protein. We found that growth cones that displayed pathfinding defects exhibited little change in their filopodial activity, whereas others without pathfinding defects exhibited an ~50% increase in their filopodial activity. Moreover, effector loop mutations that were added to the constitutively active Cdc42 (Cdc42^V12C40 and Cdc42^V12A37) exerted little influence over filopodial activity caused by Cdc42 activation but suppressed the pathfinding defects of the growth cones. Together, these data suggest that Cdc42 controls filopodial activity in axonal growth cones independently of its effects on their pathfinding.

Key words: axon guidance; Cdc42; Drosophila; filopodia; GFP; growth cone; in vivo; pathfinding

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Copyright © 2002 Society for Neuroscience  0270-6474/02/2251794-13$05.00/0

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