Developmental expression of clock genes in the Syrian hamster

Transcription/translation feedback loops consisting of multiple clock genes are thought to be essential for circadian oscillations at cellular, tissue and organismal levels. We examined the developmental expressions of three clock genes (Bmal1, Cry1 and Per1) in the Syrian hamster to probe the oscillatory properties of the suprachiasmatic nucleus (SCN) over the first 4 days after the completion of SCN neurogenesis. Samples were taken at the dam's circadian times 6, 12, and 18 daily over 4 days in constant dim light and processed for in situ hybridization using 35S-labeled RNA probes. Collection times were based on the phases of Bmal1 and Per1 rhythms in adult SCN and on an observed difference in Per1 mRNA at CT6 and 18 on postnatal day 2. For the developmental study, sections from each brain were processed in parallel for the three genes. Bmal1 was prominently expressed in the fetal SCN while Per1 and Cry1 were only weakly expressed. Transcripts of all three genes showed higher abundance just after birth. At subsequent ages, Bmal1 showed a significant decrease, while Per1 continued to be greater than prenatal levels. Significant variation was detected across circadian times for Cry1, but no circadian variation was detected for Per1 and Bmal1. Molecular oscillations equivalent to those observed in adults were not present in the fetal SCN despite evidence for an entrainable pacemaker at that time. An absence of robust oscillations during early SCN development may in part explain the strong phase-setting effects of pharmacological agents on the fetal/neonatal clock.