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Nature Cell Biology 9, 1347–1359 (1 December 2007) | doi:10.1038/ncb1654

Filopodia are required for cortical neurite initiation

Erik W. Dent , Adam V. Kwiatkowski , Leslie M. Mebane , Ulrike Philippar , Melanie Barzik , Douglas A. Rubinson , Stephanie Gupton , J. Edward Van Veen , Craig Furman , Jiangyang Zhang , Arthur S. Alberts , Susumu Mori & Frank B. Gertler

Extension of neurites from a cell body is essential to form a functional nervous system; however, the mechanisms underlying neuritogenesis are poorly understood. Ena/VASP proteins regulate actin dynamics and modulate elaboration of cellular protrusions. We recently reported that cortical axon-tract formation is lost in Ena/VASP-null mice and Ena/VASP-null cortical neurons lack filopodia and fail to elaborate neurites. Here, we report that neuritogenesis in Ena/VASP-null neurons can be rescued by restoring filopodia formation through ectopic expression of the actin nucleating protein mDia2. Conversely, wild-type neurons in which filopodia formation is blocked fail to elaborate neurites. We also report that laminin, which promotes the formation of filopodia-like actin-rich protrusions, rescues neuritogenesis in Ena/VASP-deficient neurons. Therefore, filopodia formation is a key prerequisite for neuritogenesis in cortical neurons. Neurite initiation also requires microtubule extension into filopodia, suggesting that interactions between actin-filament bundles and dynamic microtubules within filopodia are crucial for neuritogenesis.