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

Author(s): Joachim Krebs*

Journal Name: Current Topics in Medicinal Chemistry

Volume 21 , Issue 13 , 2021


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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.

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

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Article Details

VOLUME: 21
ISSUE: 13
Year: 2021
Published on: 03 June, 2021
Page: [1121 - 1128]
Pages: 8
DOI: 10.2174/1568026621666210603155653
Price: $65

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