(A) role of drosophila spitz gene in the output pathway of circadian rhythms

Abstract

A rhythm with 24 hour period is generated by a circadian pacemaker. This controls daily rhythms in behavior and physiology and sustains even in the absence of environmental time cues. The circadian clock consists of three parts, input signal, central clock oscillator, and output signal. Drosophila clock pacemaker is located in lateral neurons of brain. The molecular components of the circadian pacemaker form a transcription based negative feedback loop using positive and negative elements, respectively clock/cycle and period/timeless. And cryptochrome is an input clock gene, a major photoreceptor for behavioral circadian rhythms. Output signal from the circadian clock controls rhythmic behavior poorly understood. The signaling molecules that mediate output from pacemaker to behavior are not known, although a secreted neuropeptide, pigment dispersing factor, may be a crucial output element in Drosophila. Here, we identified a novel circadian mutant, spitz, and is a secreted ligand that can be a candidate for output signaling molecule. Hypomorphic mutations of spitz (spi) gene produced abnormal circadian rhythms in locomotor activity. Hypomorph showed normal expression of clock gene, period, but weakened especially in Lateral Neurons (LNs), circadian pacemaker. And oscillation of phospho mitogen-activated protein kinase (p-MAPK) was strongly dampened in spitz hypomorphs. And spitz was expressed broadly in larval brain including LNs and DNs. All these suggest that spitz gene can regulate output signaling pathways