Dual targets of Hugin in the modulation of a motor program in Drosophila

Innate behaviors comprise genetically hardwired motor programs frequently coupled to morphogenetic remodeling. By studying pupariation, an innate behavior that reshapes the Drosophila larval body in preparation for metamorphosis, we provide insight into the neural circuits and modulators that generate complex motor patterns and the mechanisms that coordinate them with morphological changes. We have identified the epidermis-derived protein Dilp8 as a signal required for the initiation of the pupariation motor program. Through a targeted genetic screen, we uncover three downstream neuropeptides: Mip, Capa and Hugin. We find that Hugin modulates the pupariation motor program via two parallel, receptor-specific pathways. Peripherally, Hugin signals through epidermal PK2R2 receptor, to stimulate Dilp8 release and modulate the temporal progression and contractions involved in the last stage of motor program. Concurrently, Hugin acts in the central nervous system through an alternative receptor, PK2R1, to differentially modulate the dynamics of the same motor program stage. These data identify a two-level peptidergic node and suggest the existences of a feedback loop between Dilp8 and Hugin.