Seminars and Events

Past Events

Category Seminar
Date and Time 2006-09-28 16:00 - 17:00
Venue Auditorium C1F
Speaker Makoto Sato
Affiliation Laboratory of Morphogenesis, Institute of Molecular and Cellular Biosciences, University of Tokyo
Title DWnt4 regulates the dorsoventral specificity of retinal projections in the Drosophila visual system
Poster click here to download(PDF)
Host Shigeo Hayashi
Summary Precise topographic mapping of photoreceptor neurons to their targets in the brain, 'retinotopic mapping,' is necessary for the correct interpretation of visual information received in the retina. In Drosophila, photoreceptor cells retinotopically send their axons to the first optic ganglion, the lamina. Although mechanisms that control retinotopic mapping have been extensively studied in vertebrate systems, the genetic mechanisms regulating retinotopy have not been documented in flies.

The homeobox genes of the iroquois complex are expressed in the dorsal half of the retina and specify the dorsal identity. Our finding that iroquois mutant dorsal axons misprojected to the ventral lamina suggests iroquois are the dorsal cues for the retina.
We subsequently showed that DWnt4, a secreted protein of the Wnt family, is the ventral cue for the lamina. DWnt4 is normally expressed in the ventral half of the lamina and DWnt4 protein was found along the ventral retinal axons, suggesting its involvement in retinal axon guidance. Indeed, ventral retinal axons misprojected to the dorsal lamina in DWnt4 mutant backgrounds. Ventral axons were attracted by the ectopic source of DWnt4. Dfrizzled2 and dishevelled, respectively, encode a receptor and a signaling molecule required for Wnt signaling. Mutations in both genes and inhibition of non-canonical Wnt signaling in the retina resulted in DWnt4-like phenotype, suggesting direct roles of DWnt4 and non-canonical Wnt signaling for retinal axon guidance.
Interestingly, iroquois mutant dorsal axons accumulated ectopic DWnt4 and misprojected to the ventral lamina, perhaps because dorsal axons were attracted by DWnt4 in the absence of iroquois. Since the phenotype was suppressed in iroquois Dfrizzled2 double mutant backgrounds, iroquois may attenuate the competence of Dfrizzled2 to respond to DWnt4.

In vertebrates, Eph/Ephrin family proteins play key roles in the retinotopic mapping. Similarly, genes other than iroquois and DWnt4 must be involved in the retinotopy of flies. Recently, it has been reported that Wnt3 regulates the retinotopy along the dorsoventral axis in concert with Eph/Ephrin in vertebrates. It will be interesting to see if the molecular mechanisms underlying retinotopy are conserved in vertebrates and invertebrates.
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