Notch signaling targets the Wingless responsiveness of a Ubx visceral mesoderm enhancer in Drosophila.
BACKGROUND
Members of the Notch family of receptors mediate a process known as lateral inhibition that plays a prominent role in the suppression of cell fates during development. This function is triggered by a ligand, Delta, and is implemented by the release of the intracellular domain of Notch from the membrane and by its interaction with the protein Suppressor of Hairless [Su(H)] in the nucleus. There is evidence that Notch can also signal independently of Su(H). In particular, in Drosophila, there is evidence that a Su(H)-independent activity of Notch is associated with Wingless signaling.


RESULTS
We report that Ubx(VM)B, a visceral mesoderm-specific enhancer of the Ubx gene of Drosophila, is sensitive to Notch signaling. In the absence of Notch, but not of Su(H), the enhancer becomes activated earlier and over a wider domain than in the wild type. Furthermore, the removal of Notch reduces the requirement for Disheveled-mediated Wingless signaling to activate this enhancer. This response to Notch is likely to be mediated by the dTcf binding sites in the Ubx(VM)B enhancer.


CONCLUSIONS
Our results show that, in Drosophila, an activity of Notch that is likely to be independent of Su(H) inhibits Wingless signaling on Ubx(VM)B. A possible target of this activity is dTcf. As dTcf has been shown to be capable of repressing Wingless targets, our results suggest that this repressive activity may be regulated by Notch. Finally, we suggest that Wingless signaling is composed of two steps, a down-regulation of a Su(H)-independent Notch activity that modulates the activity of dTcf and a canonical Wingless signaling event that regulates the activity of Armadillo and its interaction with dTcf.
Lawrence
N
N
Department of Zoology, University of Cambridge, CB2 3EJ, Cambridge, United Kingdom.
Langdon
T
T
Brennan
K
K
Arias
A M
AM
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D004330:Drosophila / Q000196:embryology / Q000235:genetics; D029721:Drosophila Proteins; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics*; D019476:Insect Proteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051880:Receptors, Notch; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors; D051155:Wnt1 Protein
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D011518:Proto-Oncogene Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins; C088731:Su(H) protein, Drosophila; D014157:Transcription Factors; C066177:Ubx protein, Drosophila; D051155:Wnt1 Protein; C064196:dpp protein, Drosophila; C115159:pan protein, Drosophila; C074622:wg protein, Drosophila