Serotonergic and Chemosensory Brain Areas and Sensory Ganglia Expressing Type 3 Deiodinase Mapped With Dio3Cre drivers

Thyroid hormone (triiodothyronine, T3) promotes neurodevelopment but under strict control because unconstrained exposure to T3 impairs brain and sensory functions. Thyroid hormone-inactivating type 3 deiodinase, encoded by Dio3, critically limits T3 signaling and controls diverse neural functions. Accordingly, understanding the cellular basis of T3 action requires identification of Dio3-expressing cell types but this is difficult because of low level, transient expression within the complexity of the nervous system. Here, we derived a knock-in Dio3Cre driver that sensitively labels Dio3-expressing cells in male and female mice. In this anatomical study, we identified Dio3 expression in the immature amygdala and other brain regions associated with emotion and motivation, and in serotonergic raphe nuclei, which influence many behavioral and physiological systems. Notably, expression in circumventricular organs, including the chemosensory subfornical organ and organum vasculosum laminae terminalis, suggested regulation of centers that lack a blood-brain barrier and directly sense signaling factors in the circulation. Expression in trigeminal, dorsal root, cochleovestibular, and other sensory ganglia highlighted contributions to sensory pathways. Although Dio3 expression declines during maturation, a conditional Dio3CreERt2 driver revealed neurons with T3-inducible expression in the adult brain, suggesting ongoing homeostatic functions. These Cre drivers indicate strategically located neuronal groups for control of T3 signaling in behavioral, chemosensory and sensory systems.