Dlx1 and Dlx2 Promote Interneuron GABA Synthesis, Synaptogenesis, and Dendritogenesis

Ramon Pla, Amelia Stanco, MacKenzie A. Howard, Anna N. Rubin, Daniel Vogt, Niall Mortimer, Inma Cobos, Gregory Brian Potter, Susan Lindtner, James D. Price, Alexander Nord, Axel Visel, Christoph E. Schreiner, Scott C. Baraban, David H. Rowitch, John L.R. Rubenstein

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3797-3815
Number of pages19
JournalCerebral cortex (New York, N.Y. : 1991)
Volume28
Issue number11
DOIs
StatePublished - Nov 1 2018

Fingerprint

Interneurons
gamma-Aminobutyric Acid
Synapses
Autistic Disorder
Dendrites
N-Methyl-D-Aspartate Receptors
Transcription Factors
Phenotype
Neurons
Genes

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Pla, R., Stanco, A., Howard, M. A., Rubin, A. N., Vogt, D., Mortimer, N., ... Rubenstein, J. L. R. (2018). Dlx1 and Dlx2 Promote Interneuron GABA Synthesis, Synaptogenesis, and Dendritogenesis. Cerebral cortex (New York, N.Y. : 1991), 28(11), 3797-3815. https://doi.org/10.1093/cercor/bhx241

Dlx1 and Dlx2 Promote Interneuron GABA Synthesis, Synaptogenesis, and Dendritogenesis. / Pla, Ramon; Stanco, Amelia; Howard, MacKenzie A.; Rubin, Anna N.; Vogt, Daniel; Mortimer, Niall; Cobos, Inma; Potter, Gregory Brian; Lindtner, Susan; Price, James D.; Nord, Alexander; Visel, Axel; Schreiner, Christoph E.; Baraban, Scott C.; Rowitch, David H.; Rubenstein, John L.R.

In: Cerebral cortex (New York, N.Y. : 1991), Vol. 28, No. 11, 01.11.2018, p. 3797-3815.

Research output: Contribution to journalArticle

Pla, R, Stanco, A, Howard, MA, Rubin, AN, Vogt, D, Mortimer, N, Cobos, I, Potter, GB, Lindtner, S, Price, JD, Nord, A, Visel, A, Schreiner, CE, Baraban, SC, Rowitch, DH & Rubenstein, JLR 2018, 'Dlx1 and Dlx2 Promote Interneuron GABA Synthesis, Synaptogenesis, and Dendritogenesis', Cerebral cortex (New York, N.Y. : 1991), vol. 28, no. 11, pp. 3797-3815. https://doi.org/10.1093/cercor/bhx241
Pla, Ramon ; Stanco, Amelia ; Howard, MacKenzie A. ; Rubin, Anna N. ; Vogt, Daniel ; Mortimer, Niall ; Cobos, Inma ; Potter, Gregory Brian ; Lindtner, Susan ; Price, James D. ; Nord, Alexander ; Visel, Axel ; Schreiner, Christoph E. ; Baraban, Scott C. ; Rowitch, David H. ; Rubenstein, John L.R. / Dlx1 and Dlx2 Promote Interneuron GABA Synthesis, Synaptogenesis, and Dendritogenesis. In: Cerebral cortex (New York, N.Y. : 1991). 2018 ; Vol. 28, No. 11. pp. 3797-3815.
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