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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1347-1359
Number of pages13
JournalNature cell biology
Volume9
Issue number12
DOIs
StatePublished - Dec 1 2007

ASJC Scopus subject areas

  • Cell Biology

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    Dent, E. W., Kwiatkowski, A. V., Mebane, L. M., Philippar, U., Barzik, M., Rubinson, D. A., Gupton, S., Van Veen, J. E., Furman, C., Zhang, J., Alberts, A. S., Mori, S., & Gertler, F. B. (2007). Filopodia are required for cortical neurite initiation. Nature cell biology, 9(12), 1347-1359. https://doi.org/10.1038/ncb1654