Jackson Lab Research Interests / A Function for Glia in Circadian Timing

We have been interested for a number of years in the circadian control of locomotor activity and the role of the Drosophila ebony gene in that process. Although ebony mutant populations exhibit normal eclosion rhythms, mutant individuals have arrhythmic circadian locomotor activity, suggesting a selective lesion of a clock output pathway controlling activity. The ebony gene encodes N-b-alanyl-biogenic amine synthetase (BAS), which conjugates b-alanine with one of several different biogenic amines including dopamine and serotonin to produce N-b-alanyl-biogenic amine. Consistent with this enzymatic activity, ebony mutants are known to have elevated levels of dopamine (DA) and other biogenic amines. A student in the lab, Joowon Suh, has shown that ebony mRNA and protein exhibit robust circadian changes in abundance, with a peak of expression at the beginning of the day that correlates with the initiation of locomotor activity. Oscillations of per and tim gene expression are similar in ebony mutants and the wild type, suggesting that ebony transcription is downstream of the molecular clock. Indeed, rhythms in ebony gene products are disrupted in clock mutants, indicative of a circadian control of transcription. Immunohistochemical studies demonstrate that Ebony protein is exclusively expressed in a subset of glial cells within the CNS and the optic lobes. Consistent with this localization pattern, expression of a wild-type ebony+ transgene in glial cells is sufficient for rescue of ebony mutant behavior. Interestingly, certain Ebony-containing glia express clock proteins whereas some do not but are adjacent to PER and TIM cells (glia or neurons). Furthermore, Ebony-containing cells are in close proximity to dopaminergic or serotonergic neurons of the larval and adult brains. Such a pattern of localization suggests that clock cells directly modulate the production of BAS activity in glial cells. In turn, rhythmic BAS activity may function to terminate biogenic amine action (i.e., aminergic neuronal activity), thus resulting in a circadian modulation of locomotor activity. Genetic interaction studies from the lab indicate that alterations in dopaminergic signaling may cause the arrhythmicity of ebony mutants. Whereas previous studies have suggested a role for glia in the circadian regulation of behavior, our results (Suh and Jackson, 2007) reveal a novel function for a defined population of glia in the orchestration of rhythmic locomotor activity.