This paper highlights the importance of T3 (Triiodothyronine) in development of the brain.
It makes me re-question the dependence on levothyroxine monotherapy in those born without thyroids. Can it possibly make sense?
Cereb Cortex. 2015 Nov 2. pii: bhv273. [Epub ahead of print]
Global Transcriptome Analysis of Primary Cerebrocortical Cells: Identification of Genes Regulated by Triiodothyronine in Specific Cell Types.
Gil-Ibañez P1, García-García F2, Dopazo J3, Bernal J1, Morte B4.
1Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain Center for Biomedical Research on Rare Diseases, Madrid, Spain.
2Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
3Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain Bioinformatics of Rare Diseases (BIER), CIBER de Enfermedades Raras (CIBERER), Valencia, Spain Functional Genomics Node, INB at CIPF, Valencia, Spain.
4Center for Biomedical Research on Rare Diseases, Madrid, Spain.
Thyroid hormones, thyroxine, and triiodothyronine (T3) are crucial for cerebral cortex development acting through regulation of gene expression. To define the transcriptional program under T3 regulation, we have performed RNA-Seq of T3-treated and untreated primary mouse cerebrocortical cells. The expression of 1145 genes or 7.7% of expressed genes was changed upon T3 addition, of which 371 responded to T3 in the presence of cycloheximide indicating direct transcriptional regulation. The results were compared with available transcriptomic datasets of defined cellular types. In this way, we could identify targets of T3 within genes enriched in astrocytes and neurons, in specific layers including the subplate, and in specific neurons such as prepronociceptin, cholecystokinin, or cortistatin neurons. The subplate and the prepronociceptin neurons appear as potentially major targets of T3 action. T3 upregulates mostly genes related to cell membrane events, such as G-protein signaling, neurotransmission, and ion transport and downregulates genes involved in nuclear events associated with the M phase of cell cycle, such as chromosome organization and segregation. Remarkably, the transcriptomic changes induced by T3 sustain the transition from fetal to adult patterns of gene expression. The results allow defining in molecular terms the elusive role of thyroid hormones on neocortical development.
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development; gene regulation; subplate; thyroid hormones; transcriptomics
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