Thyroid hormone regulated genes in cerebral cortex development

  1. Juan Bernal
  1. Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas y Universidad Autónoma de Madrid, and Center for Biomedical Research on Rare Diseases, Instituto de Salud Carlos III, Madrid, Spain
  1. Correspondence should be addressed to J Bernal; Email: jbernal{at}
  1. Figure 1

    Thyroid hormone and TH receptor concentrations in the human fetus. This figure contains replotted data on the concentrations of TH in coelomic and amniotic fluids (Burrow et al. 1994, Calvo et al. 2002) fetal serum (Thorpe-Beeston et al. 1991) and cerebral cortex (Kester et al. 2004) as a function of fetal age expressed in postmenstrual weeks. The lower part of the figure shows the number of T3 receptor molecules per nucleus recalculated from the original publication (Bernal & Pekonen 1984) assuming 8 pg DNA/nucleus. The inset shows the relative affinity of the human fetal receptor for triac (T3A), T3, T4, rT3 (Bernal & Pekonen 1984). The shaded bar marks the date at which the fetal thyroid gland concentrates iodine and contains thyroglobulin and iodinated compounds (Shepard 1967).

  2. Figure 2

    Model of TH transport and action in the brain. TH crosses the BBB through MCT8 and OATP1C1. MCT8 transports T4 and T3, whereas OATP1C1 is more specific for T4. MCT8 and OATP1C1 are expressed in the endothelial microvascular cells and in the membrane of astrocytes and neurons. OATP1C1 is present in the astrocytic end feet in contact with the endothelial cells, so that transport of T4 to the astrocytes is facilitated by OATP1C1. In the astrocytes, T4 is converted to T3. The T3 formed has action on the astrocytes and also on neurons after crossing the cell membranes. This last step is not strictly dependent on MCT8 as it can occur in its absence. The location of other secondary transporters for TH is shown, but their specific role has not been defined. The neurons have DIO3 activity that converts T4 and T3 to rT3 and T2, respectively.

  3. Figure 3

    Genes of primary cerebrocortical cells regulated transcriptionally by T3 classified in functional categories (Gil-Ibanez et al. 2015). Another group of 36 genes difficult to classify into functional categories are not included.

  4. Figure 4

    Scheme of cortex development and possible role of some of the genes regulated transcriptionally by T3 in the cerebrocortical cultures. Different stages of cortex development are represented: proliferation of precursors, multipolar to bipolar transition, appearance of the Cajal-Retzius cells (CR) and the subplate cells (SP) with the formation of the preplate, arrival of the first migrating neurons with the splitting of the preplate and formation of the cortical plate, and the inside out migration process to form first the deep layers (DL) 5 and 6, and then the upper layers (UL) 2 to 4. Genes regulated by T3 have been selected on the basis of specific expression at a certain developmental stage in the embryonic or P2 CR cells, the SP cells at two stages of development, specific markers genes for the DL or the UL neurons, and the extracellular matrix (EM). The extracellular matrix is represented by a shade on the marginal zone and the subplate, which stain more strongly by glycosaminoglycans, the major component of brain EM. Adapted, under the terms of the CCBY license, from Ohtaka-Maruyama C & Okado H (2015) Molecular pathways underlying projection neuron production and migration during cerebral cortical development, Frontiers in Neuroscience, volume 9, article 447.

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  1. J Endocrinol 232 R83-R97
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