Cooperative activities of drosophila DE-cadherin and DN-cadherin regulate the cell motility process of ommatidial rotation.
Ommatidial rotation is a cell motility read-out of planar cell polarity (PCP) signaling in the Drosophila eye. Although the signaling aspects of PCP establishment are beginning to be unraveled, the mechanistic aspects of the associated ommatidial rotation process remain unknown. Here, we demonstrate that the Drosophila DE- and DN-cadherins have opposing effects on rotation. DE-cadherin promotes rotation, as DE-cad mutant ommatidia rotate less than wild type or not at all. By contrast, the two DN-cadherins act to restrict this movement, with ommatidia rotating too fast in the mutants. The opposing effects of DE- and DN-cadherins result in a coordinated cellular movement, enabling ommatidia of the same stage to rotate simultaneously. Genetic interactions, phenotypic analysis and localization studies indicate that EGF-receptor and Frizzled-PCP signaling feed into the regulation of cadherin activity and localization in this context. Thus, DE- and DN-cadherins integrate inputs from at least two signaling pathways, resulting in a coordinated cell movement. A similar input into mammalian E- and N-cadherins might function in the progression of diseases such as metastatic ovarian cancer.
Mirkovic
Ivana
I
Brookdale Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, New York, NY, USA.
Mlodzik
Marek
M
D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D015820:Cadherins / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D004330:Drosophila / Q000254:growth & development*; D005123:Eye / Q000166:cytology / Q000254:growth & development*; D051157:Frizzled Receptors / Q000502:physiology; D010641:Phenotype; D015398:Signal Transduction
D015820:Cadherins; D051157:Frizzled Receptors