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The Journal of Neuroscience, October 1, 2001, 21(19):7705-7714
Soluble Guanylate Cyclase Is Required during Development for
Visual System Function in Drosophila
Sarah M.
Gibbs1,
Ann
Becker2,
Robert W.
Hardy2, and
James W.
Truman1
1 Graduate Program in Neurobiology and Behavior,
Department of Zoology, University of Washington, Seattle, Washington
98195, and 2 Departments of Biology and Neuroscience,
University of California at San Diego, La Jolla, California 92093
A requirement for nitric oxide (NO) in visual system development
has been demonstrated in many model systems, but the role of potential
downstream effector molecules has not been established. Developing
Drosophila photoreceptors express an NO-sensitive
soluble guanylate cyclase (sGC), whereas the optic lobe targets express NO synthase. Both of these molecules are expressed after photoreceptor outgrowth to the optic lobe, when retinal growth cones are actively selecting their postsynaptic partners. We have previously shown that
inhibition of the NO-cGMP pathway in vitro leads to
overgrowth of retinal axons. Here we examined flies mutant for the  subunit gene of the Drosophila sGC
(Gc1). This mutation severely reduced but did not abolish GC1 protein levels and NO-stimulated sGC activity in the developing photoreceptors. Although few mutant individuals possessed a disorganized retinal projection pattern, pharmacological NOS inhibition during metamorphosis increased this
disorganization in mutants to a greater degree than in the wild type.
Adult mutants lacked phototactic behavior, and the off-transient
component of electroretinograms was frequently absent or greatly
reduced in amplitude. Normal phototaxis and off-transient amplitude
were restored by heat shock-mediated
Gc1 expression applied during
metamorphosis but not in the adult. We propose that diminished sGC
activity in the visual system during development causes inappropriate
or inadequate formation of first-order retinal synapses, leading to
defects in visual system function and visually mediated behavior.
Key words:
phototaxis; electroretinogram; nitric oxide; cGMP; photoreceptor; invertebrate
Copyright © 2001 Society for Neuroscience 0270-6474/01/21197705-10$05.00/0
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