Molecular integration of wingless, decapentaplegic, and autoregulatory inputs into Distalless during Drosophila leg development.
The development of the Drosophila leg requires both Decapentaplegic (Dpp) and Wingless (Wg), two signals that establish the proximo-distal (PD) axis by activating target genes such as Distalless (Dll). Dll expression in the leg depends on a Dpp- and Wg-dependent phase and a maintenance phase that is independent of these signals. Here, we show that accurate Dll expression in the leg results from the synergistic interaction between two cis-regulatory elements. The Leg Trigger (LT) element directly integrates Wg and Dpp inputs and is only active in cells receiving high levels of both signals. The Maintenance (M) element is able to maintain Wg- and Dpp-independent expression, but only when in cis to LT. M, which includes the native Dll promoter, functions as an autoregulatory element by directly binding Dll. The "trigger-maintenance" model describes a mechanism by which secreted morphogens act combinatorially to induce the stable expression of target genes.
Estella
Carlos
C
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
McKay
Daniel J
DJ
Mann
Richard S
RS
D000818:Animals; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development; D029721:Drosophila Proteins / Q000235:genetics*; D005121:Extremities / Q000254:growth & development*; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics*; D006706:Homeostasis / Q000235:genetics*; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D051155:Wnt1 Protein
D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D051155:Wnt1 Protein; C117261:distal-less protein, insect; C064196:dpp protein, Drosophila; C074622:wg protein, Drosophila