Regulators of thyroid hormone availability and action in embryonic chicken brain development

Area of Science:

• Neuroscience
• Endocrinology
• Developmental Biology

Background:

• Thyroid hormones (THs) are essential for vertebrate brain development.
• TH action relies on intracellular availability of 3,5,3'-triiodothyronine (T3) and its nuclear receptors.
• TH transport, activation, and inactivation are regulated by specific transporters and deiodinases.

Purpose of the Study:

• To review the expression patterns of TH transporters, deiodinases, and receptors during embryonic chicken brain development.
• To compare these patterns with those observed in mammalian brain development.
• To elucidate mechanisms of TH uptake across developing brain barriers.

Main Methods:

• Comparative review of existing literature on TH regulators in embryonic chicken and mammalian brains.
• Analysis of expression patterns of TH transporters (MCT8, OATP1C1), deiodinases (D2, D3), and receptors.
• Examination of TH regulator localization at the developing blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB).

Main Results:

• THs and their regulators are present in the embryonic brain early in development, preceding thyroid gland function.
• At the developing BBB, TH-activating type 2 deiodinase is associated with blood vessels in chicken, but TH transporters MCT8/OATP1C1 are absent.
• At the BCSFB, TH-inactivating type 3 deiodinase and transporters MCT8/OATP1C1 are co-expressed in both birds and mammals.

Conclusions:

• TH uptake mechanisms across developing brain barriers show both conserved patterns and species-specific differences between chickens and mammals.
• Understanding these differences is crucial for interpreting species-specific responses to genetic manipulations of TH regulators.
• TH action in the developing brain is tightly regulated by a complex interplay of transporters, deiodinases, and receptors.