title: Differential maturation of circadian rhythms in clock gene proteins in the suprachiasmatic nucleus and the pars tuberalis during mouse ontogeny.
abstract: Circadian rhythms of many body functions in mammals are controlled by a master pacemaker, residing in the hypothalamic suprachiasmatic nucleus (SCN), which synchronises peripheral oscillators. The SCN and peripheral oscillators share several components of the molecular clockwork and comprise transcriptional activators (BMAL1 and CLOCK/NPAS2) and inhibitors (mPER1/2 and mCRY1/2). Here we compared the ontogenetic maturation of the clockwork in the SCN and pars tuberalis (PT). The PT is a peripheral oscillator that strongly depends on rhythmic melatonin signals. Immunoreactions for clock gene proteins were determined in the SCN and PT at four different timepoints during four differential stages of mouse ontogeny: foetal (embryonic day 18), newborn (2-day-old), infantile (10-day-old), and adult. In the foetal SCN, levels of immunoreactions of all clock proteins were significantly lower than adult levels except for BMAL1. In the newborn SCN the clock protein immunoreactions had not yet reached adult levels, but the infantile SCN showed similar levels of immunoreactions as the adult. In contrast, immunoreactions for all clock gene proteins in the foetal PT were as intense as in newborn, infantile and adult, and showed the same phase. As the foetal pineal gland is not yet capable of rhythmic melatonin production, the rhythms in clock gene proteins in the foetal PT are presumably dependent on the maternal melatonin signal. Thus, our data provide the first evidence that maternal melatonin is important for establishing and maintaining circadian rhythms in a foetal peripheral oscillator.
authors.affiliation: Dr Senckenbergische Anatomie, Emmy Noether Research Group, Goethe University, Frankfurt, Germany.
authors.forename: Nariman
authors.initials: N
authors.lastname: Ansari
authors.forename: Manuel
authors.initials: M
authors.lastname: Agathagelidis
authors.forename: Choogon
authors.initials: C
authors.lastname: Lee
authors.forename: Horst-Werner
authors.initials: HW
authors.lastname: Korf
authors.forename: Charlotte
authors.initials: C
authors.lastname: von Gall
mesh_terms: D056930:ARNTL Transcription Factors; D000375:Aging / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001683:Biological Clocks / Q000235:genetics*; D056926:CLOCK Proteins; D002452:Cell Count; D002940:Circadian Rhythm / Q000235:genetics*; D056931:Cryptochromes; D005260:Female; D005420:Flavoproteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D016011:Normal Distribution; D056950:Period Circadian Proteins; D010903:Pituitary Gland, Anterior / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D056931:Cryptochromes; D005420:Flavoproteins; D047908:Intracellular Signaling Peptides and Proteins; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; C538961:Bmal1 protein, mouse; C539023:Per1 protein, mouse; C538944:Clock protein, mouse