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 advanced transcriptomic sequencing and high frequency resolution during the initiation, maintenance and recovery of circannual timing for Siberian hamster energy balance to delineate the molecular architecture of a neuroendocrine seasonal clock. Three distinct phases of transcript changes were identified, and deiodinase type-3 (Dio3) expression was activated during the initiation phase. Targeted mutation of Dio3 resulted in a shortening of the circannual interval timer period. Hamsters that exhibit a form of naturally occurring disruption in Dio3 eliminated circannual interval timing. Our work demonstrates that the evolutionary conserved changes in hypothalamic tanycytes expression of Dio3 is critical for timing seasonal life history traits in chordates. Overall design: To investigate molecular changes occuring in the distinct regions of the hypothalamus. Siberian hamsters were held in long days (LD) or short days (SD) for up to 32-weeks. At 4-week intervals, animals were sacrificed and the piutiary and hpyothalamic nuclei were dissected. Microdissections were homogenised and RNA was extracted using the RNEasy plus mini kit. following this transcript abundance was assesed using the cDNA-PCR sequencing kit (SQK-PCB109, Oxford Nanopore).