Hypothalamic deiodinase type-3 establishes the period of circannual interval timing in mammals

Animals respond to environmental cues to time phenological events, but the intrinsic mechanism of circannual timing remains elusive. We used transcriptomic sequencing and frequent sampling, during three distinct phases (induction, maintenance and recovery) of circannual interval timing for Djungarian hamster energy balance, to investigate the molecular architecture of a neuroendocrine seasonal clock. Our study identified three distinct phases of transcript changes, with deiodinase type-3 (Dio3) expression activated during the early induction phase. Subsequent work demonstrated that targeted mutation of Dio3 resulted in a shorter period for circannual interval timing. Hamsters that exhibit naturally disrupted Dio3 expression do not show any change in body mass or pelage. Our work demonstrates that changes in Dio3 induction is essential for setting the period of circannual interval timing.