Cellular expression domains of type 3 deiodinase in the meninges, choroid plexus, tanycytes and barrier tissues of the brain

Thyroid hormone is necessary to stimulate mammalian brain development but its action must be limited to avoid damage arising from unregulated stimulation. Type 3 deiodinase, a thyroid hormone-degrading enzyme encoded by Dio3, constrains thyroid hormone exposure in the brain and has primarily been described in neuronal populations. However, detection is difficult because of low, transient expression, often in specialized cell populations. Here, using Dio3Cre-mediated labeling with a sensitive fluorescent reporter, we uncovered Dio3 expression in non-neuronal cell types in blood-cerebrospinal fluid (CSF) and blood-brain barriers during development in mice. These barriers control solute transport, suggesting that Dio3 regulates thyroid hormone availability at these cellular interfaces between brain tissues and hormone-bearing fluids. Dio3 expression was detected in the arachnoid barrier in the meninges, the membranes surrounding the brain, and in the epithelial layer of the choroid plexus, which regulates solute exchange with CSF. Transcriptome analyses corroborated early Dio3 expression in these tissues, beginning even before barrier function matures. Dio3 expression was also detected in tanycytes lining the third ventricle and in pericytes associated with capillaries at the neurovascular interface. These findings suggest a role for Dio3 in regulating thyroid hormone availability at key interfaces of CSF and blood with immature brain tissues.