Expression of Clock and Clock-Driven Genes in the Rat Suprachiasmatic Nucleus during Late Fetal and Early Postnatal Development

Apr 11, 2006Journal of biological rhythms

Daily rhythm genes in the rat brain's internal clock during late fetal and early newborn stages

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Abstract

At postnatal day (P) 1, rhythms in Per1, Bmal1, and arginine-vasopressin (AVP) gene expression are present in the rat suprachiasmatic nucleus (SCN).

Rhythms in clock gene expression were not detectable at embryonic day (E) 19 but began to develop between E20 and P3.
At E20, only Per1 expression showed signs of rhythmicity, while other clock genes and AVP expression did not.
By P1, rhythmic expression of Per1, Bmal1, and AVP was observed, with a developing rhythm in Per2 and no rhythm in Cry1.
The Per1 rhythm was only slightly pronounced, and the Bmal1 rhythm had an atypical shape compared to adult patterns.
At P2, significant rhythms in Per1, Per2, and Bmal1 were present, alongside a forming rhythm in Cry1, but not in Clock.
The findings suggest that the development of clock gene rhythms primarily occurs postnatally and may involve additional mechanisms for AVP gene expression.

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The SCN as a site of the circadian clock itself exhibits rhythmicity. A molecular clockwork responsible for the rhythmicity consists of clock genes and their negative and positive transcriptional-translational feedback loops. The authors' previous work showed that rhythms in clock gene expression in the rat SCN were not yet detectable at embryonic day (E) 19 but were already present at postnatal day (P) 3. The aim of the present study was to elucidate when during the interval E19-P3 the rhythms start to develop in clock gene expression and in clock-controlled, namely in arginine-vasopressin (AVP), gene expression. Daily profiles of Per1, Per2, Cry1, Bmal1, and Clock mRNA and of AVP heteronuclear (hn) RNA as an indicator of AVP gene transcription were assessed in the SCN of fetuses at E20 and of newborn rats at P1 and P2 by the in situ hybridization method. At E20, formation of a rhythm in Per1 expression was indicated, but no rhythms in expression of other clock genes or of the AVP gene were detected. At P1, rhythms in Per1, Bmal1, and AVP and a forming rhythm in Per2 but no rhythm in Cry1 expression were present in the SCN. The Per1 mRNA rhythm was, however, only slightly pronounced. The Bmal1 mRNA rhythm, although pronounced, exhibited still an atypical shape. Only the AVP hnRNA rhythm resembled that of adult rats. At P2, marked rhythms of Per1, Per2, and Bmal1 and a forming rhythm of Cry1, but not of Clock, expression were present. The data suggest that rhythms in clock gene expression for the most part develop postnatally and that other mechanisms besides the core clockwork might be involved in the generation of the rhythmic AVP gene expression in the rat SCN during early ontogenesis.

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Expression of Clock and Clock-Driven Genes in the Rat Suprachiasmatic Nucleus during Late Fetal and Early Postnatal Development

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