Nitric Oxide and Cyclic GMP Regulate Retinal Patterning in the Optic Lobe of Drosophila

Abstract

The photoreceptors of Drosophila express a nitric oxide-sensitive guanylate cyclase during the first half of metamorphosis, when postsynaptic elements in the optic lobe are being selected. Throughout this period, the optic lobes show NADPH-diaphorase activity and stain with an antibody to nitric oxide synthase (NOS). The NOS inhibitor L-NAME, the NO scavenger PTIO, the sGC inhibitor ODQ, and methylene blue, which inhibits NOS and guanylate cyclase, each caused the disorganization of retinal projections and extension of photoreceptor axons beyond their normal synaptic layers in vitro. The disruptive effects of L-NAME were prevented with the addition of 8-bromo-cGMP. These results suggest NO and cGMP act to stabilize retinal growth cones at the start of synaptic assembly.

Regulation of multimers via truncated isoforms: a novel mechanism to control nitric-oxide signaling

“…NO regulates cell proliferation in the imaginal discs of developing larvae (Kuzin et al 1996) and in embryos (Wingrove and O'Farrell 1999), participates in the development of the visual system (Gibbs and Truman 1998;Gibbs 2003), induces vesicle release at the neuromuscular junction of larvae (Wildemann and Bicker 1999), controls epithelial fluid secretion by the Malpigian tubules (Dow et al 1994;Broderick et al 2003), triggers the immune response against bacterial pathogens (Nappi et al 2000), induces arrest of nuclear divisions in early embryo in response to oxygen deprivation (DiGregorio et al 2001), and mediates hypoxia-dependent exploratory behavioral responses in larvae (Wingrove and O'Farrell 1999) and hypoxia-induced stasis in embryos (Teodoro and O'Farrell 2003). This wide range of processes mediated by NO requires tight regulation of its production in response to different stimuli.…”

“…In mammals, these changes include blood-vessel relaxation, immune response, cell cycle control, and neurotransmission. In Drosophila, NO has been implicated in visual-system development, immunity, behavior, response to hypoxia, osmoregulation, and regulation of cell cycle progression during development (Dow et al 1994;Kuzin et al 1996Kuzin et al , 2000Gibbs and Truman 1998;Wingrove and O'Farrell 1999;Nappi et al 2000;DiGregorio et al 2001;Teodoro and O'Farrell 2003).…”

Nitric oxide directly regulates gene expression during Drosophila development: need some gas to drive into metamorphosis?: Figure 1.

“…In insects, its diverse range of functions include regulation of renal fluid production, cell proliferation, synapse formation, and innate immunity (Kuzin et al 1996;Gibbs and Truman 1998;Kean et al 2002;Foley and O'Farrell 2003). In many of these cases, NO exerts its function through binding to the heme moiety of soluble guanylate cyclase to stimulate cyclic GMP synthesis.…”

Nitric oxide contributes to induction of innate immune responses to gram-negative bacteria inDrosophila

“…In contrast to the genetic rearrangements and clonal selection processes that underlie adaptive immunity, innate immunity relies on the functions of germ-line encoded gene products. Nitric oxide (NO) is a highly reactive molecule with innate immune functions as well as roles in responses to hypoxia and CNS development (Dawson et al 1991;Bredt and Snyder 1994;Gibbs and Truman 1998;Wingrove and O'Farrell 1999;Bogdan 2001). NO is produced in mammalian macrophages by a nitric oxide synthase isoform (iNOS/NOS2), which is strongly up-regulated following infection (MacMicking et al 1997).…”