Filopodia are required for cortical neurite initiation

Nat Cell Biol. 2007 Dec;9(12):1347-59. doi: 10.1038/ncb1654. Epub 2007 Nov 18.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / physiology
  • Cells, Cultured
  • Cerebral Cortex / cytology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology
  • Laminin / physiology
  • Mice
  • Mice, Knockout
  • Microfilament Proteins / genetics
  • Microfilament Proteins / physiology
  • Microtubule-Associated Proteins
  • Microtubules / physiology
  • Mutation
  • Myosin Type II / antagonists & inhibitors
  • Myosins / biosynthesis
  • NADPH Dehydrogenase / biosynthesis
  • Neurites / physiology*
  • Neurons / physiology*
  • Neurons / ultrastructure
  • Phosphoproteins / genetics
  • Phosphoproteins / physiology
  • Pseudopodia / physiology*


  • Actins
  • Cell Adhesion Molecules
  • DNA-Binding Proteins
  • ENA-VASP proteins
  • Evl protein, mouse
  • Laminin
  • Microfilament Proteins
  • Microtubule-Associated Proteins
  • Myo10 protein, mouse
  • Phosphoproteins
  • vasodilator-stimulated phosphoprotein
  • Dia2 protein, mouse
  • NADPH Dehydrogenase
  • Myosin Type II
  • Myosins