High impact information on Med

• Furthermore, we present genetic and biochemical evidence that the brk silencer serves as a direct target for a protein complex consisting of the Smad homologs Mad/Medea and the zinc finger protein Schnurri [1].
• Dpp signals via the SMAD proteins Mad and Medea [2].
• Screens for binding factors yielded Tinman itself and the Smad4 homolog Medea [3].
• Here we show that Hiw binds to the Smad protein Medea (Med) [4].
• Indeed, ectopic expression of a dad-LacZ enhancer trap revealed that the Dpp pathway was upregulated in slmb somatic clones and, consistent with this, ectopic accumulation of the co-Smad protein, Medea, was recorded [5].

Biological context of Med

• MEDEA is localized in the cytoplasm, is not regulated by phosphorylation, and requires physical association with MAD for nuclear translocation [6].
• However, Mad is essential in the germline for oogenesis whereas Medea is dispensable [6].
• This enhancer integrates positive signals, mediated by the Decapentaplegic signaling effector protein Medea, with the repressor activity of Brinker [7].
• However, recently it has been shown that a complex of the Drosophila Smad proteins, Mad and Medea, binds with high affinity to silencer elements that repress brinker and bag of marbles in response to Dpp signaling [8].
• The proximal BMP-responsive element (PBE) in the Smad6 promoter is important for the transcriptional activation by BMPs and contains a 28-base pair GC-rich sequence including four overlapping copies of the GCCGnCGC-like motif, which is a binding site for Drosophila Mad and Medea [9].

Anatomical context of Med

• Furthermore, inactivating MEDEA mutations prevent nuclear translocation either by preventing interaction with MAD or by trapping MAD/MEDEA complexes in the cytosol [6].
• Genetic analysis suggests that Medea may have two independently mutable functions in patterning the embryonic ectoderm [10].
• Our data demonstrate that nuclear accumulation of the co-SMAD Medea requires a BMP signal during blastoderm and gastrula stages [11].
• 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 [12].
• As part of the study of this species, two diploid cell lines (2n = 12) of the Med-fly were established in vitro on two different culture media [13].

Associations of Med with chemical compounds

• Binding was also affected by alanine substitutions in Mad and Med at a subset of basic residues within and flanking helix 2, indicating a contribution to binding of the GRCGNC and GTCT sites [8].

Regulatory relationships of Med

• Screens for dpp interactions with maternally expressed genes have identified loss of function mutations in Mothers against dpp and Medea [14].

Other interactions of Med

• In the wing primordium, loss of Medea most severely affects regions receiving low DPP signal [6].
• Furthermore, we show that dSMAD2 complexes with MEDEA only in the presence of ATR-I and PUNT. dSmad2 is expressed in the imaginal disks and in the outer proliferation centre of the larval brain, suggesting that it may have important proliferative and patterning roles during Drosophila development [15].
• We show that a weak, homozygous-viable sog mutant is enhanced to lethality by reduction in the activities of the Smad family members Mad or Medea, and that the lethality is caused by defects in the molecular specification and subsequent cellular differentiation of the dorsal-most cell type, the amnioserosa [16].
• In marked GSCs mutant for Med and punt, two essential Bmp signal transducers, bam transcription is also elevated [17].

References