title: Filopodia are required for cortical neurite initiation.
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.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Erik W
authors.initials: EW
authors.lastname: Dent
authors.forename: Adam V
authors.initials: AV
authors.lastname: Kwiatkowski
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Mebane
authors.forename: Ulrike
authors.initials: U
authors.lastname: Philippar
authors.forename: Melanie
authors.initials: M
authors.lastname: Barzik
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Rubinson
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gupton
authors.forename: J Edward
authors.initials: JE
authors.lastname: Van Veen
authors.forename: Craig
authors.initials: C
authors.lastname: Furman
authors.forename: Jiangyang
authors.initials: J
authors.lastname: Zhang
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Alberts
authors.forename: Susumu
authors.initials: S
authors.lastname: Mori
authors.forename: Frank B
authors.initials: FB
authors.lastname: Gertler
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D007797:Laminin / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000502:physiology; D008869:Microtubule-Associated Proteins; D008870:Microtubules / Q000502:physiology; D009154:Mutation; D024462:Myosin Type II / Q000037:antagonists & inhibitors; D009218:Myosins / Q000096:biosynthesis; D009252:NADPH Dehydrogenase / Q000096:biosynthesis; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D011554:Pseudopodia / Q000502:physiology*; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D000199:Actins; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; C092744:ENA-VASP proteins; C102177:Evl protein, mouse; D007797:Laminin; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; C409064:Myo10 protein, mouse; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein; C508552:Dia2 protein, mouse; D009252:NADPH Dehydrogenase; D024462:Myosin Type II; D009218:Myosins