Ena/VASP Is Required for neuritogenesis in the developing cortex.
Mammalian cortical development involves neuronal migration and neuritogenesis; this latter process forms the structural precursors to axons and dendrites. Elucidating the pathways that regulate the cytoskeleton to drive these processes is fundamental to our understanding of cortical development. Here we show that loss of all three murine Ena/VASP proteins, a family of actin regulatory proteins, causes neuronal ectopias, alters intralayer positioning in the cortical plate, and, surprisingly, blocks axon fiber tract formation during corticogenesis. Cortical fiber tract defects in the absence of Ena/VASP arise from a failure in neurite initiation, a prerequisite for axon formation. Neurite initiation defects in Ena/VASP-deficient neurons are preceded by a failure to form bundled actin filaments and filopodia. These findings provide insight into the regulation of neurite formation and the role of the actin cytoskeleton during cortical development.
Kwiatkowski
Adam V
AV
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Rubinson
Douglas A
DA
Dent
Erik W
EW
Edward van Veen
J
J
Leslie
Jonathan D
JD
Zhang
Jiangyang
J
Mebane
Leslie M
LM
Philippar
Ulrike
U
Pinheiro
Elaine M
EM
Burds
Aurora A
AA
Bronson
Roderick T
RT
Mori
Susumu
S
Fässler
Reinhard
R
Gertler
Frank B
FB
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D019521:Body Patterning / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D002678:Chimera; D005260:Female; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009421:Nervous System Malformations / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009434:Neural Pathways / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D016501:Neurites / Q000378:metabolism* / Q000648:ultrastructure; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism / Q000648:ultrastructure; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein