RT Journal Article
T1 Thyroid hormone regulation of gene expression in the developing rat fetal cerebral cortex: Prominent role of the Ca2+/calmodulin-dependent protein kinase IV pathway
A1 Morte, Beatriz
A1 Díez, Diego
A1 Ausó, Eva
A1 Belinchón, Mónica
A1 Gil Ibáñez, Pilar
A1 Grijota Martínez, María Carmen
A1 Navarro, Daniela
A1 Morreale de Escobar, Gabriella
A1 Berbel, Pere
A1 Bernal, Juan
AB Thyroid hormones influence brain development through regulation of gene expression mediated by nuclear receptors. Nuclear receptor concentration increases rapidly in the human fetus during the secondtrimester,aperiod of high sensitivity of the brain to thyroidhormones.In the rat, the equivalent period is the last quarter of pregnancy. However, little is known about thyroid hormone action in the fetal brain, and in rodents, most thyroid hormone-regulated genes have been identified during the postnatal period. To identify potential targets of thyroid hormone in the fetal brain,weinduced maternal and fetal hypothyroidism by maternal thyroidectomy followed by antithyroid drug (2-mercapto-1-methylimidazole) treatment. Microarray analysis identified differentially expressed genes in the cerebral cortex of hypothyroid fetuses on d 21 after conception. Gene function analysis revealed genes involved in the biogenesis of the cytoskeleton, neuronal migration and growth, and branching of neurites. Twenty per cent of the differentially expressed genes were related to each other centered on the Ca2+ and calmodulin-activated kinase (Camk4) pathway.Camk4was regulated directly by T3 in primary cultured neurons from fetal cortex, and the Camk4 protein was also induced by thyroid hormone. No differentially expressed genes were recovered when euthyroid fetuses from hypothyroid mothers were compared with fetuses from normal mothers. Although the resultsdonot rule out a specific contribution from the mother, especially at earlier stages of pregnancy, they indicate that the main regulators of thyroid hormone-dependent, fetal brain gene expression near term are the fetal thyroid hormones.
PB Oxford University Press
SN 0013-7227
YR 2010
FD 2010
LK https://hdl.handle.net/20.500.14352/92372
UL https://hdl.handle.net/20.500.14352/92372
LA eng
NO Morte, Beatriz, et al. «Thyroid Hormone Regulation of Gene Expression in the Developing Rat Fetal Cerebral Cortex: Prominent Role of the Ca2+/Calmodulin-Dependent Protein Kinase IV Pathway». Endocrinology, vol. 151, n.o 2, febrero de 2010, pp. 810-20. https://doi.org/10.1210/en.2009-0958.
NO Ministerio de Ciencia e Innovación (España)
NO European Commission
NO Centro de Investigación Biomédica en Enfermedades Raras (España)
NO Consejo Superior de Investigaciones Científicas (España)
NO The Japanese Society for the Promotion of Science
DS Docta Complutense
RD 8 abr 2025