Ena/VASP Is Required for Neuritogenesis in the Developing Cortex

• Published in: Neuron (Cambridge, Mass.) Vol. 56; no. 3; pp. 441 - 455
• Main Authors: Kwiatkowski, Adam V., Rubinson, Douglas A., Dent, Erik W., Edward van Veen, J., Leslie, Jonathan D., Zhang, Jiangyang, Mebane, Leslie M., Philippar, Ulrike, Pinheiro, Elaine M., Burds, Aurora A., Bronson, Roderick T., Mori, Susumu, Fässler, Reinhard, Gertler, Frank B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.11.2007; Elsevier Limited
• Subjects: Actin Cytoskeleton - metabolism; Animals; Body Patterning - genetics; Cell adhesion & migration; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell culture; Cell Differentiation - genetics; Cell Movement - genetics; Cells, Cultured; Cerebral Cortex - cytology; Cerebral Cortex - embryology; Cerebral Cortex - metabolism; Chimera; Defects; DEVBIO; Embryos; Female; Growth Cones - metabolism; Growth Cones - ultrastructure; Histology; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; MOLNEURO; Mutation - genetics; Nervous System Malformations - genetics; Nervous System Malformations - metabolism; Nervous System Malformations - physiopathology; Neural Pathways - cytology; Neural Pathways - embryology; Neural Pathways - metabolism; Neurites - metabolism; Neurites - ultrastructure; Neurons; Phosphoproteins - genetics; Phosphoproteins - metabolism; Proteins; Pseudopodia - metabolism; Pseudopodia - ultrastructure; DEVBIO; MOLNEURO
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2007.09.008

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.