摘要：SummaryCircadian rhythms persist in almost all organisms and are crucial for maintaining appropriate timing in physiology and behaviour. Here, we describe a mouse mutant where the central mammalian pacemaker, the suprachiasmatic nucleus (SCN), has been genetically ablated by conditional deletion of the transcription factorZfhx3in the developing hypothalamus. Mutants were arrhythmic over the light-dark cycle and in constant darkness. Moreover, rhythms of metabolic parameters were ablatedin vivoalthough molecular oscillations in the liver maintained some rhythmicity. Despite disruptions to SCN cell identity and circuitry, mutants could still anticipate food availability, yet other zeitgebers - including social cues from cage-mates - were ineffective in restoring rhythmicity although activity levels in mutants were altered. This work highlights a critical role forZfhx3in the development of a functional SCN, while its genetic ablation further defines the contribution of SCN circuitry in orchestrating physiological and behavioral responses to environmental signals.Graphical abstractDisplay OmittedHighlights•Deletion of Zfhx3 in developing hypothalamus leads to behavioral arrhythmicity•SCN cell identity is absent while other retinal targets and visual functions remain•Rhythms in metabolic functions are lost while some molecular rhythms in liver persist•Conditional mutants can respond to food availability and other environmental cuesBiological sciences; Physiology; Molecular biology; Neuroscience
