title: Ontogeny of circadian organization in the rat.
abstract: The mammalian circadian system is orchestrated by a master pacemaker in the brain, but many peripheral tissues also contain independent or quasi-independent circadian oscillators. The adaptive significance of clocks in these structures must lie, in large part, in the phase relationships between the constituent oscillators and their micro- and macroenvironments. To examine the relationship between postnatal development, which is dependent on endogenous programs and maternal/environmental influences, and the phase of circadian oscillators, the authors assessed the circadian phase of pineal, liver, lung, adrenal, and thyroid tissues cultured from Period 1-luciferase (Per1-luc ) rat pups of various postnatal ages. The liver, thyroid, and pineal were rhythmic at birth, but the phases of their Per1-luc expression rhythms shifted remarkably during development. To determine if the timing of the phase shift in each tissue could be the result of changing environmental conditions, the behavior of pups and their mothers was monitored. The circadian phase of the liver shifted from the day to night around postnatal day (P) 22 as the pups nursed less during the light and instead ate solid food during the dark. Furthermore, the phase of Per1-luc expression in liver cultures from nursing neonates could be shifted experimentally from the day to the night by allowing pups access to the dam only during the dark. Peak Per1-luc expression also shifted from midday to early night in thyroid cultures at about P20, concurrent with the shift in eating times. The phase of Per1-luc expression in the pineal gland shifted from day to night coincident with its sympathetic innervation at around P5. Per1-luc expression was rhythmic in adrenal cultures and peaked around the time of lights-off throughout development; however, the amplitude of the rhythm increased at P25. Lung cultures were completely arrhythmic until P12 when the pups began to leave the nest. Taken together, the data suggest that the molecular machinery that generates circadian oscillations matures at different rates in different tissues and that the phase of at least some peripheral organs is malleable and may shift as the organ's function changes during development.
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Shin
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Biscoe
authors.forename: Rika
authors.initials: R
authors.lastname: Numano
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Gallaspy
authors.forename: Stacy
authors.initials: S
authors.lastname: Soulsby
authors.forename: Evagelia
authors.initials: E
authors.lastname: Papadimas
authors.forename: Pinar
authors.initials: P
authors.lastname: Pezuk
authors.forename: Susan E
authors.initials: SE
authors.lastname: Doyle
authors.forename: Hajime
authors.initials: H
authors.lastname: Tei
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Sakaki
authors.forename: Gene D
authors.initials: GD
authors.lastname: Block
authors.forename: Michael
authors.initials: M
authors.lastname: Menaker
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001683:Biological Clocks; D001921:Brain / Q000378:metabolism*; D002940:Circadian Rhythm; D005260:Female; D006720:Homozygote; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009991:Oscillometry; D056950:Period Circadian Proteins; D051381:Rats; D013493:Suprachiasmatic Nucleus / Q000378:metabolism; D013997:Time Factors
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C539024:Per1 protein, rat; D056950:Period Circadian Proteins