Nap1-regulated neuronal cytoskeletal dynamics is essential for the final differentiation of neurons in cerebral cortex.
The cytoskeletal regulators that mediate the change in the neuronal cytoskeletal machinery from one that promotes oriented motility to one that facilitates differentiation at the appropriate locations in the developing neocortex remain unknown. We found that Nck-associated protein 1 (Nap1), an adaptor protein thought to modulate actin nucleation, is selectively expressed in the developing cortical plate, where neurons terminate their migration and initiate laminar-specific differentiation. Loss of Nap1 function disrupts neuronal differentiation. Premature expression of Nap1 in migrating neurons retards migration and promotes postmigratory differentiation. Nap1 gene mutation in mice leads to neural tube and neuronal differentiation defects. Disruption of Nap1 retards the ability to localize key actin cytoskeletal regulators such as WAVE1 to the protrusive edges where they are needed to elaborate process outgrowth. Thus, Nap1 plays an essential role in facilitating neuronal cytoskeletal changes underlying the postmigratory differentiation of cortical neurons, a critical step in functional wiring of the cortex.
Yokota
Yukako
Y
UNC Neuroscience Center, Department of Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Ring
Colleen
C
Chong
Rockie
R
Pevny
Larysa
L
Anton
E S
ES
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement; D002540:Cerebral Cortex / Q000166:cytology* / Q000201:enzymology; D004622:Embryo, Mammalian / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D051379:Mice; D008817:Mice, Mutant Strains; D008855:Microscopy, Electron, Scanning / Q000379:methods; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology; D013997:Time Factors; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D019208:Brain-Derived Neurotrophic Factor; C078332:Nck protein; D015513:Oncogene Proteins; D051300:Wiskott-Aldrich Syndrome Protein Family