Vip expression was rhythmic at both E19 and E21, although the rhythm was very weak compared to other evaluated rhythmic genes. Therefore, the weak circadian rhythm in Vip expression is beta-Carotene present before the clock mechanism is fully functional. VIP is an important mediator among SCN cells and is responsible for increasing the robustness of their oscillations. In the fetal rat central nervous system, VIP receptors are abundant already by E11. Activation of VIP receptors leads to elevation of P-CREB levels transcription of genes containing CRE in their promoter. Therefore, the above mentioned c-fos and Avp expression rhythms observed at E19 may be related to Vip rhythmicity via this mechanism. Additionally, VIP may play a role in synchronizing SCN neurons during the developmental period when the synaptic web is lacking. However, the amplitude of Vip expression rhythm is very low in the fetal SCN and it is thus not clear whether has any functional relevance. During fetal SCN development, transcript levels changed between E19 and E21. The initially high expression levels of Per2 and Bmal1, i.e., genes which were constitutively expressed at E19, declined with fetal age in correlation with the initiation of circadian regulation. In contrast, expression levels of genes that were rhythmically expressed at E19 increased with fetal age, in correlation with clock development. These findings are in accordance with results of our previous study, in which clock gene expression in the SCN was detected by in situ Tetrandrine hybridization ; of the genes examined in the previous study, Per2 and Bmal1 were expressed with at the highest levels at E19. The results of the present study confirm that this previous finding was indeed due to differences in transcript levels and was not related to a methodological problems related with the properties of the probes used for the in situ hybridization. Apparently, these data also suggest that with the initiation of circadian control, rhythmicity is generated via suppression of high Per2 and Bmal1 transcription and induction of low Per1 and Cry1 transcription.