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Filopodia are required for cortical neurite initiation
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Journal Article
Filopodia are required for cortical neurite initiation
2007
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Analysis
/ Animals
/ Biomedical and Life Sciences
/ Cell Adhesion Molecules - genetics
/ Cell Adhesion Molecules - physiology
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - physiology
/ Mice
/ Microfilament Proteins - genetics
/ Microfilament Proteins - physiology
/ Microtubule-Associated Proteins
/ Mutation
/ Myosin Type II - antagonists & inhibitors
/ NADPH Dehydrogenase - biosynthesis
/ Neurons
/ Phosphoproteins - physiology
/ Proteins
