INSP(3) RECEPTOR IS ESSENTIAL FOR GROWTH AND DIFFERENTIATION BUT NOT FOR VISION IN DROSOPHILA

Phospholipase C (PLC) is the focal point for two major signal transduc tion pathways: one initiated by G protein-coupled receptors and the ot her by tyrosine kinase receptors. Active PLC hydrolyzes phosphatidylin ositol bisphosphate (PIP2) into the two second messengers inositol 1,4 ,5-trisphosphate (InsP(3)) and diacyl glycerol (DAG). DAG activates pr otein kinase C, and InsP(3) mobilizes calcium from intracellular store s via the InsP(3) receptor. Changes in [Ca2+](i) regulate the function of a wide range of target proteins, including ion channels, kinases, phosphatases, proteases, and transcription factors (Berridge, 1993). I n the mouse, there are three InsP(3)R genes, and type 1 InsP(3)R mutan ts display ataxia and epileptic seizures (Matsumoto et al., 1996). In Drosophila, only one InsP(3) receptor (InsP(3)R) gene is known, and it is expressed ubiquitously throughout development (Hasan and Rosbash, 1992; Yoshikawa et al., 1992; Raghu and Hasan, 1995). Here, we charact erize Drosophila InsP(3)R mutants and demonstrate that the InsP(3)R is essential for embryonic and larval development. Interestingly, matern al InsP(3)R mRNA is sufficient for progression through the embryonic s tages, but larval organs show asynchronous and defective cell division s, and imaginal discs arrest early and fail to differentiate. We also generated adult mosaic animals and demonstrate that phototransduction, a model PLC pathway thought to require InsP(3)R, does not require Ins P(3)R for signaling.