DWnt4 regulates the dorsoventral specificity of retinal projections in the Drosophila melanogaster visual system.
In Drosophila melanogaster, the axons of retinal photoreceptor cells extend to the first optic ganglion, the lamina, forming a topographic representation. Here we show that DWnt4, a secreted protein of the Wnt family, is the ventral cue for the lamina. In DWnt4 mutants, ventral retinal axons misprojected to the dorsal lamina. DWnt4 was normally expressed in the ventral half of the developing lamina and DWnt4 protein was detected along ventral retinal axons. Dfrizzled2 and dishevelled, respectively, encode a receptor and a signaling molecule required for Wnt signaling. Mutations in both genes caused DWnt4-like defects, and both genes were autonomously required in the retina, suggesting a direct role of DWnt4 in retinal axon guidance. In contrast, iroquois homeobox genes are the dorsal cues for the retina. Dorsal axons accumulated DWnt4 and misprojected to the ventral lamina in iroquois mutants; the phenotype was suppressed in iroquois Dfrizzled2 mutants, suggesting that iroquois may attenuate the competence of Dfrizzled2 to respond to DWnt4.
Sato
Makoto
M
Laboratory of Morphogenesis, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Bunkyo, Tokyo 113-0032, Japan.
Umetsu
Daiki
D
Murakami
Satoshi
S
Yasugi
Tetsuo
T
Tabata
Tetsuya
T
D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D000818:Animals; D001369:Axons / Q000502:physiology; D003001:Cloning, Molecular; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster; D051157:Frizzled Receptors / Q000235:genetics / Q000502:physiology; D006023:Glycoproteins / Q000502:physiology*; D007150:Immunohistochemistry; D009154:Mutation / Q000502:physiology; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D017956:Photoreceptor Cells, Invertebrate / Q000502:physiology; D012160:Retina / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014795:Visual Pathways / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D051153:Wnt Proteins / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D051157:Frizzled Receptors; D006023:Glycoproteins; D010750:Phosphoproteins; D051153:Wnt Proteins; C454442:Wnt4 protein, Drosophila; C000606588:dsh protein, Drosophila