Since the first appearance of life on earth, organisms have had to adapt to alternating phases of light and darkness triggered by the complete revolution of the planet on its axis every 24 hours. One adaptation was to acquire an internal clock that would dictate the appropriate biological process for the specific time of day, e.g. ensuring that they avoid activity during the hottest parts of the day, or while predators are around. Nowadays human beings battle with their intrinsic clock when doing shift work or coping with jetlag after traveling across time zones and malfunctioning circadian clocks have been linked to several diseases, including cancer.

Similarly to humans, Drosophila melanogaster exhibit circadian patterns of activity, which are controlled by clock proteins in a network of clock neurons located in the central nervous system. However, the molecular pathways by which fly and mammalian clock neurons communicate with each other to generate robust and self-sustaining behavioral rhythms are not clear.

To identify additional genes that could include factors that send or receive signals for intercellular communication in the circadian neuronal network, we used a GAL4/UAS mis-expression screen in Drosophila clock neurons. Candidate lines were selected upon showing disrupted patterns of locomotor activity in constant darkness. Cloning of the region of insertion of the EP738 and EP1751 lines led to the isolation of the stretch and Mef2 genes respectively, which are responsible for the phenotypes observed.

The present study describes: (i) a potential role for stretch in the regulation of circadian behavior of Drosophila, and (ii) how Mef2, a gene with a well-established role in muscle development, is required for robust circadian locomotor activity, and concomitant molecular rhythms in the pacemaker neurons of fruit flies.