COUP-TF1 Modulates Thyroid Hormone Action in an Embryonic Stem Cell Model of Cortical Pyramidal Neuronal Differentiation.

COUP-TF1 Modulates Thyroid Hormone Action in an Embryonic Stem Cell Model of Cortical Pyramidal Neuronal Differentiation.

Thyroid. 2017 Dec 05;:

Authors: Teng X, Liu YY, Teng W, Brent GA

Abstract
BACKGROUND: Thyroid hormone is critical for normal brain development and acts in a spatial and temporal specific pattern. Thyroid hormone excess, or deficiency, can lead to irreversible impairment of brain and sensory development. COUP-TF1, expressed early in neuronal development, is essential to achieve normal brain structure. Thyroid hormone stimulation of gene expression is inversely correlated with the level of COUP-TF1 expression.
METHODS: We utilized an in vitro method of differentiating mouse embryonic stem (mES) cells into cortical neurons to study the influence of COUP-TF1 on thyroid hormone signaling in brain development. We cultured and differentiated mES cells in specific conditioned media and obtained a high percentage of nestin-positive progenitor neurons in the first stage, and cortical neurons in the second stage, with characteristic neuronal firing.
RESULTS: The number of nestin-positive progenitors, as determined by FACS analysis, was significantly greater with triiodothyronine (T3) treatment, compared to control (p<0.05). T3 enhanced the expression of cortical neuron marker (TBR1 and RC3) mRNAs. After COUP-TF1 knockdown, the number of nestin-positive progenitors was reduced, compared to control (p<0.05), but the number increased with T3 treatment. We measured the mRNA of cortical neuronal gene markers after COUP-TF1 knockdown. In the presence of T3, the peak expression of neuron markers EMX1, TBR1, CamKIV and RC3 mRNA was earlier, at day 18 of differentiation, compared to control cells, at day 22. Furthermore, after COUP-TF1 knockdown, T3 induction of RC3 and TBR1 mRNA was significantly enhanced, compared to cells expressing COUP-TF1.
CONCLUSIONS: These results indicate that COUP-TF1 plays an important role in modulating the timing and magnitude of T3-stimulated gene expression required for normal corticogenesis.

PMID: 29205104 [PubMed - as supplied by publisher]

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