Thyroid hormone promotes fetal neurogenesis

Area of Science:

• Neuroscience
• Developmental Biology
• Endocrinology

Background:

• Maternal low thyroxine (T4) levels in early pregnancy are linked to offspring neurodevelopmental outcomes.
• The precise mechanisms by which neural cells are vulnerable to maternal T4 levels during fetal development are not fully understood.

Purpose of the Study:

• To investigate the role of thyroid hormones in human neural precursor cell differentiation and neurogenesis.
• To elucidate the molecular pathways involved in thyroid hormone action in the developing brain.

Main Methods:

• Utilized induced pluripotent stem cells (iPSCs) from a patient with a loss-of-function mutation in the MCT8 transporter.
• Employed single-cell, spatial, and bulk transcriptomics on MCT8-deficient cerebral organoids and human neural precursor cells (NPCs).
• Analyzed the expression of deiodinase enzymes and thyroid hormone nuclear receptors.

Main Results:

• Thyroid hormones induce transcriptional changes promoting dorsal trajectory progression in human neural precursor cells.
• Optimal thyroid hormone levels are necessary for NPC differentiation into neurons.
• Intracellular T4 activation via type 2 deiodinase and nuclear receptors regulates NPC division and cell cycle progression.

Conclusions:

• Thyroxine (T4) is essential for fetal neurogenesis and proper brain development.
• MCT8 transporter and intracellular T4 activation are critical for thyroid hormone signaling in neural cells.
• Highlights the importance of adequate maternal thyroid hormone levels during pregnancy for offspring neurodevelopment.