Circadian clocks control temporal structure in practically all organisms an
d on all levels of biology, from gene expression to complex behaviour and c
ognition. Over the last decades, research has begun to unravel the physiolo
gical and, more recently, molecular mechanisms that underlie this endogenou
s temporal programme. The generation of circadian rhythms can be explained,
at the molecular level, by a model based upon a set of genes and their pro
ducts which form an autoregulating negative feedback loop. The elements con
tributing to this transcriptional feedback appear to be conserved from inse
cts to mammals. Here, we summarize the process of the genetic and molecular
research that led to 'closing the molecular loop'. Now that the reductioni
st approach has led to the description of a detailed clock model at the mol
ecular level, further insights into the circadian system can be provided by
combining the extensive knowledge gained from decades of physiological res
earch with molecular tools, thereby reconstructing the clock within the org
anism and its environment. We describe experiments combining old and new to
ols and show that they constitute a powerful approach to understanding the
mechanisms that lead to temporal structure in complex behaviour. (C) Inra/E
lsevier, Paris.