Filopodia are required for cortical neurite initiation.
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.
Dent
Erik W
EW
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Kwiatkowski
Adam V
AV
Mebane
Leslie M
LM
Philippar
Ulrike
U
Barzik
Melanie
M
Rubinson
Douglas A
DA
Gupton
Stephanie
S
Van Veen
J Edward
JE
Furman
Craig
C
Zhang
Jiangyang
J
Alberts
Arthur S
AS
Mori
Susumu
S
Gertler
Frank B
FB
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
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