THE BMP PATHWAY IS RECRUITED BY DIFFERENT CIRCADIAN CLUSTERS TO COMMUNICATE TIME OF DAY INFORMATION IN ADULT Drosophila

CERIANI, M. FERNANDA; POLCOWÑUK, SOFÍA

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Circadian behavior is controlled by an endogenous clock. In Drosophila, this clock resides in about 150 neurons; among them, the sLNvs are particularly relevant to set the free-running period. To improve our understanding about the communication among different circadian clusters we carried out a miss-expression screen in the sLNvs. This approach uncovered a long period phenotype mutant that affected the levels of a positive regulator of the BMP pathway, a highly conserved retrograde signaling pathway that influences synaptic connectivity through transcriptional control.Taking advantage of different genetic tools we observed that the activation of the signaling cascade (through expression of a transcription factor or constitutive activated versions of receptors) triggers a long period phenotype, while cluster-specific downregulation of specific ligands triggered loss of rhythmicity under constant conditions compared to controls (statistical analysis included Kruskal Wallis test). To characterize further the steps leading to pathway activation, we examined pMad staining through immunohistochemistry on wild type brains. Interestingly, despite pMad is found exclusively in the nucleus in non-circadian neurons, pMAD is in the cytoplasm in the small and large LNvs suggesting a cluster specific-regulation. In that regard, we explored the possibility that overexpression of the DPP and GBB ligands in specific circadian neurons could increase the amount of pMAD in the nucleus of LNvs neurons. We found that DPP overexpression generates an increase in pMAD nuclear levels exclusively in the LNvs while GBB has no effect (Statistical analysis included a One-way ANOVA).These results show that not only the BMP pathway is active in LNvs neurons, but also they differentially respond to specific ligands. This finding opens the provocative possibility that the BMP pathway is recruited by different circadian clusters to communicate time information and for fine tuning clock properties.