Hikaru genki protein is secreted into synaptic clefts from an early stage of synapse formation in Drosophila.

The development of neural circuits is regulated by a large number of factors that are localized at distinct neural sites. We report here the localization of one of these factors, hikaru genki (hig) protein, at synaptic clefts in the pupal and adult nervous systems of Drosophila. In hig mutants, unusually frequent bursting activity of the muscles and abnormal motor behavior during the adult stage suggest the misfunction of neuromuscular circuitry. Our immunohistochemical analyses revealed that hig protein, produced by neurons, is secreted from the presynaptic terminals into the spaces between the presynaptic and postsynaptic terminals. In addition, we have found that the localization of this protein in the synaptic spaces temporally correlates with its functional requirement during a critical period that occurs in the middle stage of pupal formation, a period when a number of dendrite and axon growth cones meet to form synapses. These findings indicate that hig protein functions in the formation of functional neural circuits from the early stages of synapse formation.