title: Ena/VASP Is Required for neuritogenesis in the developing cortex.
abstract: 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.
authors.affiliation: Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Adam V
authors.initials: AV
authors.lastname: Kwiatkowski
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Rubinson
authors.forename: Erik W
authors.initials: EW
authors.lastname: Dent
authors.forename: J
authors.initials: J
authors.lastname: Edward van Veen
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Leslie
authors.forename: Jiangyang
authors.initials: J
authors.lastname: Zhang
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Mebane
authors.forename: Ulrike
authors.initials: U
authors.lastname: Philippar
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Pinheiro
authors.forename: Aurora A
authors.initials: AA
authors.lastname: Burds
authors.forename: Roderick T
authors.initials: RT
authors.lastname: Bronson
authors.forename: Susumu
authors.initials: S
authors.lastname: Mori
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
authors.forename: Frank B
authors.initials: FB
authors.lastname: Gertler
mesh_terms: 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
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein