| First Author | Richard S | Year | 2020 |
| Journal | iScience | Volume | 23 |
| Issue | 3 | Pages | 100899 |
| PubMed ID | 32092701 | Mgi Jnum | J:338657 |
| Mgi Id | MGI:6717875 | Doi | 10.1016/j.isci.2020.100899 |
| Citation | Richard S, et al. (2020) A Pivotal Genetic Program Controlled by Thyroid Hormone during the Maturation of GABAergic Neurons. iScience 23(3):100899 |
| abstractText | Mammalian brain development critically depends on proper thyroid hormone signaling, via the TRalpha1 nuclear receptor. The downstream mechanisms by which TRalpha1 impacts brain development are currently unknown. In order to investigate these mechanisms, we used mouse genetics to induce the expression of a dominant-negative mutation of TRalpha1 specifically in GABAergic neurons, the main inhibitory neurons in the brain. This triggered post-natal epileptic seizures and a profound impairment of GABAergic neuron maturation in several brain regions. Analysis of the transcriptome and TRalpha1 cistrome in the striatum allowed us to identify a small set of genes, the transcription of which is upregulated by TRalpha1 in GABAergic neurons and which probably plays an important role during post-natal maturation of the brain. Thus, our results point to GABAergic neurons as direct targets of thyroid hormone during brain development and suggest that many defects seen in hypothyroid brains may be secondary to GABAergic neuron malfunction. |
