Interpretation of the wingless gradient requires signaling-induced self-inhibition.
In a classical view of development, a cell can acquire positional information by reading the local concentration of a morphogen independently of its neighbors. Accordingly, in Drosophila, the morphogen Wingless produced in the wing's prospective distal region activates target genes in a dose-dependent fashion to organize the proximodistal pattern. Here, we show that, in parallel, Wingless triggers two nonautonomous inhibitory programs that play an important role in the establishment of positional information. Cells flanking the source of Wingless produce a negative signal (encoded by notum) that inhibits Wingless signaling in nearby cells. Additionally, in response to Wingless, all prospective wing cells produce an unidentified signal that dampens target gene expression in surrounding cells. Thus, cells influence each other's response to Wingless through at least two modes of lateral inhibition. Without lateral inhibition, some cells acquire ectopic fates. Lateral inhibition may be a general mechanism behind the interpretation of morphogen gradients.
Piddini
Eugenia
E
MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
Vincent
Jean-Paul
JP
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D060466:Axin Protein; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000254:growth & development* / Q000378:metabolism; D005246:Feedback; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D014921:Wings, Animal / Q000254:growth & development; D051155:Wnt1 Protein / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; C118000:Axn protein, Drosophila; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D051155:Wnt1 Protein; C117261:distal-less protein, insect; C095064:vg protein, Drosophila; C074622:wg protein, Drosophila