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 adapt...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2007-05, Vol.54 (3), p.429-445
Main Authors: Yokota, Yukako, Ring, Colleen, Cheung, Rocky, Pevny, Larysa, Anton, E.S.
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing
Animals
Brain-Derived Neurotrophic Factor - pharmacology
Cell Differentiation - physiology
Cell Movement
Cerebral Cortex - cytology
Cerebral Cortex - enzymology
DEVBIO
Embryo, Mammalian - ultrastructure
Gene Expression Regulation, Developmental - drug effects
Gene Expression Regulation, Developmental - physiology
Immunoprecipitation
In Situ Hybridization
Mice
Mice, Mutant Strains
Microscopy, Electron, Scanning - methods
Migration
MOLNEURO
Neurons
Neurons - cytology
Neurons - drug effects
Neurons - physiology
Oncogene Proteins - genetics
Oncogene Proteins - physiology
Plasmids
Protein Structure, Tertiary
Protein Transport - physiology
Proteins
Time Factors
Wiskott-Aldrich Syndrome Protein Family - metabolism
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Summary: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.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2007.04.016