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

Thyroid hormone is required for brain development but under constraint because its unregulated action can damage target tissues. 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 Dio3 Cre-mediated cell 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 embryonic and neonatal development in mice. These barriers control solute transport, suggesting that Dio3 regulates thyroid hormone availability at cellular barriers between hormone-bearing fluids and the brain. Dio3 expression was detected in the arachnoid barrier layer in the meninges, the membranes surrounding the brain, and in the epithelial layer of the choroid plexus, which regulates solute exchange with CSF. RNA 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 in the mediobasal hypothalamus, in a restricted portion of the glia limitans at the ventral hypothalamus, and in pericytes at the neurovascular interface. These findings suggest a role for Dio3 in regulating thyroid hormone availability at cellular interfaces with fluids that transport thyroid hormone in the immature brain.