A roundabout mutation alters the pace of the clock.

J BERNI, E BECKWITH AND MF CERIANI.

Sandestin, Florida, USA

Congreso; X meeting Society for Biological Rhythms; 2006

Society for Biological Rhythms

In recent years great efforts have been directed to the dissection of the cell-autonomous circadian oscillator in Drosophila. However, less information is available regarding how this molecular oscillator controls one of the most studied clock outputs: the rhythmic rest-activity cycles. We have identified a viable hypomorph allele of roundabout, robohy, where the period of locomotor activity is shortened. From its role in axon pathfinding during embryogenesis, we anticipated developmental defects in clock-relevant neuronal structures. However, robohy produced only subtle defects on the neuronal circuits expressing the pigment dispersing factor, essential for the control of rhythmic behavior, suggesting that alterations are not developmental. The presence of ROBO in the adult fly brain strengthened the possibility of a novel role for ROBO at this post-developmental stage. In fact, the early translocation of PERIOD to the nucleus observed in robohy pacemaker cells indicated that shortened activity rhythms are due to alterations in the molecular oscillator. Behavioral periodicity was also affected by genetic interaction between robohy and abelson, a molecule involved in the canonical ROBO signaling pathway. ABELSON expression within circadian relevant structures suggests a role for molecules involved in this pathway in setting the properties of the molecular oscillator. Unlike all previous reports of period-affecting mutations, we present a novel mechanism affecting clock function associated to a molecule involved in circuit assembly and maintenance.