The Sno Oncogene Antagonizes Wingless Signaling during Wing Development in Drosophila

Abstract

The Sno oncogene (Snoo or dSno in Drosophila) is a highly conserved protein and a well-established antagonist of Transforming Growth Factor-β signaling in overexpression assays. However, analyses of Sno mutants in flies and mice have proven enigmatic in revealing developmental roles for Sno proteins. Thus, to identify developmental roles for dSno we first reconciled conflicting data on the lethality of dSno mutations. Then we conducted analyses of wing development in dSno loss of function genotypes. These studies revealed ectopic margin bristles and ectopic campaniform sensilla in the anterior compartment of the wing blade suggesting that dSno functions to antagonize Wingless (Wg) signaling. A subsequent series of gain of function analyses yielded the opposite phenotype (loss of bristles and sensilla) and further suggested that dSno antagonizes Wg signal transduction in target cells. To date Sno family proteins have not been reported to influence the Wg pathway during development in any species. Overall our data suggest that dSno functions as a tissue-specific component of the Wg signaling pathway with modest antagonistic activity under normal conditions but capable of blocking significant levels of extraneous Wg, a role that may be conserved in vertebrates.

DrosophilaCORL is required for Smad2-mediated activation of Ecdysone Receptor expression in the mushroom body

“…In the embryonic CNS, CORL expression precedes Sno by two developmental stages (12 versus 14) but given its ubiquity in this tissue, Sno is almost certainly present in cells that express CORL beginning at stage 14, although this has not been formally shown. Within the third instar larval CNS, the only cells with significant Sno expression are in the optic lobe (Quijano et al, 2010) where CORL is not expressed.…”

Fat facets deubiquitylation of Medea/Smad4 modulates interpretation of a Dpp morphogen gradient

“…RNA in situ double labeling of embryos with rho or dpp or sog and lacZ cDNAs or antibody double labeling with anti-pMad and anti-lacZ were as described previously (Takaesu et al, 2002;Shimmi et al, 2005). Fluorescence double labeling of embryos followed methods of Quijano et al (Quijano et al, 2010) using anti-Hnt and anti-lacZ. Additional antibodies employed in unfertilized eggs and embryos were anti-Flag (Sigma) and anti-Bonus (Beckstead et al, 2001).…”

Wg Signaling via Zw3 and Mad Restricts Self-Renewal of Sensory Organ Precursor Cells in Drosophila

“…Although these transgenes are also lethal with MS1096.Gal4, third instar disks can be examined (Quijano et al 2010). As for Sca-Mad, we found that MS1096-Mad disks (Figure 4, D and E) displayed variable pMad-Gsk with no disks lacking expression.…”

“…General stocks including lacZ and GFP balancers as well as FLP/FRT stocks for loss-of-function clones are described in FlyBase (Tweedie et al 2009). Genetic analyses of wings and disks followed Takaesu et al (2005) and Quijano et al (2010).…”

“…The presence of ectopic mechanosensory bristles on the margin is attributed to ectopic canonical Wg signaling. Wings with Sca-dAxinDRGS that have modestly reduced Wg signaling [dAxinDRGS is less potent than CA-Zw3 (Quijano et al 2010)] and no impact on pMad-Gsk expression also did not contain defects in sensilla or chemosensory bristles ( Figure 3D, Table S3D). We attribute occasional gaps in the stout mechanosensory bristle row to a reduction in canonical Wg signaling.…”