Tcf7l2 transcription factor is required for the maintenance, but not the initial specification, of the neurotransmitter identity in the caudal thalamus
| Autor: | Jaeseung Yoon, Quy‐Hoai Nguyen, Ji‐eun Jeong, Sojeong Seong, Won-Bae Park, Hong‐Nhung Tran, Yongsu Jeong, Kwanghee Baek |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
endocrine system endocrine system diseases Thalamus Biology Inhibitory postsynaptic potential 03 medical and health sciences Diencephalon chemistry.chemical_compound Glutamatergic 0302 clinical medicine Neurotransmitter Transcription factor Neurons Neurotransmitter Agents 030104 developmental biology nervous system chemistry Excitatory postsynaptic potential GABAergic Transcription Factor 7-Like 2 Protein Neuroscience 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Developmental Dynamics. 249:646-655 |
| ISSN: | 1097-0177 1058-8388 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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