The Influence of Thyroid Hormone on Ca²⁺ Signaling Pathways During Embryonal Development

Title:The Influence of Thyroid Hormone on Ca²⁺ Signaling Pathways During Embryonal Development

Volume: 21 Issue: 13

Author(s): Joachim Krebs*

Affiliation:

• NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen,Germany

Keywords: Thyroid hormone, CaMKIV, Neurexin, SYT2, SRG1, PMCA1a, TRPC1, COUP-TF1, Brain development, Embryonal stem cells, Hypothyroidism.

Abstract: Thyroid hormones influence brain development through the regulation of gene expression. Ca²⁺-dependent gene expression is a major pathway controlled by the Ca²⁺/calmodulin-dependent protein kinase IV (CaMKIV), which in turn is induced by the thyroid hormone T₃, as also demonstrated in a mouse embryonic stem cell line. In addition, T₃ controls the expression of neurexin, synaptotagmin2 (SYT2), synaptotagmin-related gene1 (SRG1), and a number of other genes involved in neurotransmitter release in a Ca²⁺-dependent manner. It has been noticed that the development of dopaminergic neurons by evoking significant calcium entry occurs through TRPC calcium channels. It was also demonstrated that the T₃-mediated development of an early neuronal network is characteristic for depolarizing GABAergic neurons concomitant with intracellular calcium transients. An important aspect of T₃-dependent regulation of gene expression in the developing brain is its modulation by the transcription activator COUP-TF1. Regulation of alternative splicing by CaMKIV is another important aspect for embryonal neural development since it can lead to the expression of PMCA1a, the neuronal-specific isoform of the plasma membrane calcium pump. Maternal hypothyroidism or CaMKIV deficiency can have a severe influence on fetal brain development.

Cite this article as:

Krebs Joachim*, The Influence of Thyroid Hormone on Ca²⁺ Signaling Pathways During Embryonal Development, Current Topics in Medicinal Chemistry 2021; 21 (13) . https://dx.doi.org/10.2174/1568026621666210603155653