Identifying genes affecting locomotor behavior in Drosophila.

MF CERIANI

Janelia Farm, Virginia, USA

Workshop; 2006 Meeting of HHMI International Research Scholars.; 2006

Howard Hughes Medical Institute

In Drosophila a number of key processes such as emergence from the pupal case, locomotor activity, olfaction, and feeding are under circadian regulation.  Specifically we are interested in unraveling the molecular mechanisms underlying the circadian control of rest/activity cycles.  To that end we have explored two complementary strategies, a forward genetic screen based on the yeast GAL4/UAS system, and a candidate approach looking at the impact of defects in the circadian circuitry derived from mutations in potentially relevant genes in rhythmic control of behavior.  Among the latter, we have identified a viable allele of roundabout, robohy, where the period of locomotor activity is shortened.  From its role in axon-pathfinding, we anticipated developmental defects in clock-relevant structures.  However, robohy produced minor defects on the circuits essential for control of rhythmic behavior.  ROBO´s presence in the adult brain strengthened the possibility of a novel role for ROBO at this post-developmental stage.  Early translocation of PERIOD to the nucleus observed in robohy pacemaker cells indicated that shortened activity rhythms derived from alterations in the molecular oscillator.  Behavioral periodicity was also affected by genetic interaction between robohy and abelson (abl), a molecule involved in the canonical ROBO signaling pathway.  ABL expression within circadian relevant structures suggests a role for this pathway in setting the properties of the oscillator.  In a parallel study we have taken advantage of flies exhibiting a distinctive arrhythmic phenotype due to mutation of the calcium-dependent voltage-gated potassium channel slowpoke (slo) to examine the activity of specific neuronal populations in circadian control of behavior.  Molecular oscillations in the core pacemaker cells were properly running in the null mutant.  However, altered neuronal function associated to the null mutation specifically impaired PDF accumulation in the dorsal protocerebrum, and in turn, desynchronized oscillations in the dorsal clusters.  We thus demonstrated that control of rhythmic behavior depends on a highly complex neuronal network whose activity coordinates the molecular oscillators within that network.