title: Development of the circadian clockwork in the kidney.
abstract: The circadian molecular clock is an internal time-keeping system composed of centrally synchronized tissue-level pacemakers. Here, we explored the ontogeny of the clock machinery in the developing kidney. Pregnant rats were housed at 12-12 h light-dark cycles. Offsprings were killed at 4-h intervals on embryonic day 20 and at postnatal weeks 1, 4, and 12. Canonical clock gene (Clock, Bmal1, Rev-erbα, Cry1, Cry2, Per1, Per2) and kidney-specific clock-controlled gene (αENaC, SGK1, NHE3, AVPR2) expression was profiled by RT-PCR. To investigate the role of nutritional cues, the feeding pattern was modified postpartum. Clock, Rev-erbα, Per2, αENaC, SGK1, NHE3, and AVPR2 showed circadian expression at the end of intrauterine development. By 1 week, all genes oscillated with a distinct acrophase shift toward the time of peak feeding activity. Daily 4-hour withdrawal of mothers induced a 12-hour phase shift of Clock and Bmal1 expression, while disrupting oscillations of the other genes. After weaning, oscillation phases shifted back toward the adult pattern, which was fully expressed at 12 weeks. Thus, functional circadian molecular clockwork evolves in the late fetal and early postnatal kidney. During the nursing period, oscillations are entrained by nutritional cues. The coupling of the circadian expression of tubular regulators of fluid and electrolyte excretion to the feeding-entrained clockwork may be important to maintain homeostasis during this critical period.
authors.affiliation: 1] Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany [2] Nephrological Research Laboratory of the Hungarian Academy of Science and the First Department of Pediatrics, Semmelweis University, Semmelweis, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Mészáros
authors.affiliation: Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Pruess
authors.affiliation: Nephrological Research Laboratory of the Hungarian Academy of Science and the First Department of Pediatrics, Semmelweis University, Semmelweis, Hungary.
authors.forename: Attila J
authors.initials: AJ
authors.lastname: Szabó
authors.affiliation: Department of Psychology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Matthias
authors.initials: M
authors.lastname: Gondan
authors.affiliation: Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Ritz
authors.affiliation: Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Schaefer
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D057906:Circadian Clocks / Q000235:genetics; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D003463:Cues; D004435:Eating; D005247:Feeding Behavior; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006706:Homeostasis; D007668:Kidney / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D007774:Lactation; D008425:Maternal Behavior; D008426:Maternal Deprivation; D017440:Photoperiod; D011247:Pregnancy; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014886:Weaning
chemical_list: D056925:Circadian Rhythm Signaling Peptides and Proteins