Dlx1 and Dlx2 Promote Interneuron GABA Synthesis, Synaptogenesis, and Dendritogenesis.
Cereb Cortex
; 28(11): 3797-3815, 2018 11 01.
Article
em En
| MEDLINE
| ID: mdl-29028947
ABSTRACT
The postnatal functions of the Dlx1&2 transcription factors in cortical interneurons (CINs) are unknown. Here, using conditional Dlx1, Dlx2, and Dlx1&2 knockouts (CKOs), we defined their roles in specific CINs. The CKOs had dendritic, synaptic, and survival defects, affecting even PV+ CINs. We provide evidence that DLX2 directly drives Gad1, Gad2, and Vgat expression, and show that mutants had reduced mIPSC amplitude. In addition, the mutants formed fewer GABAergic synapses on excitatory neurons and had reduced mIPSC frequency. Furthermore, Dlx1/2 CKO had hypoplastic dendrites, fewer excitatory synapses, and reduced excitatory input. We provide evidence that some of these phenotypes were due to reduced expression of GRIN2B (a subunit of the NMDA receptor), a high confidence Autism gene. Thus, Dlx1&2 coordinate key components of CIN postnatal development by promoting their excitability, inhibitory output, and survival.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sinapses
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Fatores de Transcrição
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Córtex Cerebral
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Proteínas de Homeodomínio
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Neurônios GABAérgicos
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Ácido gama-Aminobutírico
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Interneurônios
Limite:
Animals
Idioma:
En
Revista:
Cereb Cortex
Assunto da revista:
CEREBRO
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos