Mutations of CNTNAP1 led to defects in neuronal development.
JCI Insight
; 5(21)2020 11 05.
Article
em En
| MEDLINE
| ID: mdl-33148880
ABSTRACT
Mutations of CNTNAP1 were associated with myelination disorders, suggesting the role of CNTNAP1 in myelination processes. Whether CNTNAP1 may have a role in early cortical neuronal development is largely unknown. In this study, we identified 4 compound heterozygous mutations of CNTNAP1 in 2 Chinese families. Using mouse models, we found that CNTNAP1 is highly expressed in neurons and is located predominantly in MAP2+ neurons during the early developmental stage. Importantly, Cntnap1 deficiency results in aberrant dendritic growth and spine development in vitro and in vivo, and it delayed migration of cortical neurons during early development. Finally, we found that the number of parvalbumin+ neurons in the cortex and hippocampus of Cntnap1-/- mice is strikingly increased by P15, suggesting that excitation/inhibition balance is impaired. Together, this evidence elucidates a critical function of CNTNAP1 in cortical development, providing insights underlying molecular and circuit mechanisms of CNTNAP1-related disease.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Moléculas de Adesão Celular Neuronais
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Córtex Cerebral
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Embrião de Mamíferos
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Hipocampo
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Mutação
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Neurônios
Limite:
Animals
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Female
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Humans
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Male
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Newborn
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article