Tcf7l2 transcription factor is required for the maintenance, but not the initial specification, of the neurotransmitter identity in the caudal thalamus

Hong Nhung Tran, Wonbae Park, Sojeong Seong, Ji eun Jeong, Quy Hoai Nguyen, Jaeseung Yoon, Kwanghee Baek, Yongsu Jeong

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Background: Dysfunction of GABAergic and glutamatergic neurons in the brain, which establish inhibitory and excitatory networks, respectively, may cause diverse neurological disorders. The mechanism underlying the determination of GABAergic vs. glutamatergic neurotransmitter phenotype in the caudal diencephalon remains largely unknown. Results: In this study, we investigated the consequence of Tcf7l2 (transcription factor 7-like 2) ablation on the neurotransmitter identity of GABAergic and glutamatergic neurons in the caudal diencephalon. We identified positive and negative activity in the control of glutamatergic and GABAergic neuronal gene expression by Tcf7l2. Loss of Tcf7l2 did not alter the initial acquisition of the neurotransmitter identity in thalamic neurons. However, glutamatergic thalamic neurons failed to maintain their excitatory neurotransmitter phenotype in the absence of Tcf7l2. Moreover, a subset of Tcf7l2-deficient thalamic neurons underwent a glutamatergic to GABAergic neurotransmitter identity switch. Our data indicate that Tcf7l2 may promote glutamatergic neuronal differentiation and repress GABAergic neurotransmitter identity in the caudal thalamus. Conclusions: This study provides evidence for a novel and crucial role of Tcf7l2 in the molecular mechanism by which the neurotransmitter identity of glutamatergic thalamic neurons is established. Our findings exemplify a clear case of neurotransmitter identity regulation that is partitioned into initiation and maintenance phases.

Original languageEnglish
Pages (from-to)646-655
Number of pages10
JournalDevelopmental Dynamics
Volume249
Issue number5
DOIs
Publication statusPublished - 1 May 2020

Keywords

  • Tcf7l2
  • mouse
  • neurotransmitter
  • thalamus

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