dSno Facilitates Baboon Signaling in the Drosophila Brain by Switching the Affinity of Medea Away From Mad and Toward dSmad2

Abstract

A screen for modifiers of Dpp adult phenotypes led to the identification of the Drosophila homolog of the Sno oncogene (dSno). The dSno locus is large, transcriptionally complex and contains a recent retrotransposon insertion that may be essential for dSno function, an intriguing possibility from the perspective of developmental evolution. dSno is highly transcribed in the embryonic central nervous system and transcripts are most abundant in third instar larvae. dSno mutant larvae have proliferation defects in the optic lobe of the brain very similar to those seen in baboon (Activin type I receptor) and dSmad2 mutants. This suggests that dSno is a mediator of Baboon signaling. dSno binds to Medea and Medea/dSno complexes have enhanced affinity for dSmad2. Alternatively, Medea/dSno complexes have reduced affinity for Mad such that, in the presence of dSno, Dpp signaling is antagonized. We propose that dSno functions as a switch in optic lobe development, shunting Medea from the Dpp pathway to the Activin pathway to ensure proper proliferation. Pathway switching in target cells is a previously unreported mechanism for regulating TGFb signaling and a novel function for Sno/Ski family proteins.

Informatics approaches to understanding TGFβ pathway regulation

“…Alternatively, Sno proteins in M. musculus, D. melanogaster and C. elegans have been shown to facilitate TGFb signaling. For example, in D. melanogaster, the dSno (SnooFlyBase) mutant phenotype mimics the loss of Activin signaling, and biochemical studies have revealed that dSno facilitates Activin signaling by shifting the affinity of the Co-Smad Medea away from Mad (the BMP-dedicated R-Smad) and towards dSmad2 (Smox -FlyBase) (Takaesu et al, 2006). Taken together, these data suggest that the influence of Sno proteins on TGFb signaling is probably tissue specific.…”

The role of Dpp and its inhibitors during eggshell patterning inDrosophila

“…This cDNA closely resembles dSnoI as described by Takaesu et al (Takaesu et al, 2006). The 1360 bp amplified fragment was cloned in pCR-TOPO 2.1 and sequenced.…”

“…In particular, we characterized the ovarian function of the Drosophila homolog of the Sno oncogene. dSno has recently been shown to antagonize TGF-␤ signaling in nervous system and in wing development (Takaesu et al, 2006;Ramel et al, 2007).…”

“…7). During brain development in flies (Takaesu et al, 2006) and in several contexts in vertebrates (for a review, see Luo, 2004) Sno is involved in the control of cell proliferation that has been shown to be crucially dependent on the relative levels of TGF-␤ and EGF signaling (for a review, see Siegel and Massague, 2003). It is conceivable that for spatial patterning of the follicular epithelium dSno uses regulatory elements that are derived from a more basic function in the control of cell proliferation in other tissues.…”

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

“…Stage of lethality tests were as described (Takaesu et al, 2006). Alignments and phylogenetic trees were as described previously (Konikoff et al, 2010).…”