title: Generation of multiple antagonistic domains along the proximodistal axis during Drosophila leg development.
abstract: homothorax (hth) is a Drosophila member of the Meis family of homeobox genes. hth function is required for the nuclear localization of the Hox cofactor Extradenticle (EXD). We show here that there is also a post-transcriptional control of HTH by exd: exd activity is required for the apparent stability of the HTH protein. In leg imaginal discs, hth expression is limited to the domain of exd function and this domain is complementary to the domain in which the Wingless (WG) and Decapentaplegic (DPP) signals are active. We demonstrate that WG and DPP act together through their targets Distal-less (Dll) and dachshund (dac) to restrict hth expression, and therefore EXD's nuclear localization, to the most proximal regions of the leg disc. Furthermore, there is a reciprocal repression exerted by HTH on these and other DPP and WG downstream targets that restricts their expression to non-hth-expressing cells. Thus, there exists in the leg disc a set of mutually antagonistic interactions between proximal cells, which we define as those that express hth, and distal cells, or those that do not express hth. In addition, we show that dac negatively regulates Dll. We suggest that these antagonistic relationships help to convert the WG and DPP activity gradients into discreet domains of gene expression along the proximodistal axis.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Integrated Program in Cellular, Molecular and Biophysical Studies, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: M
authors.initials: M
authors.lastname: Abu-Shaar
authors.forename: R S
authors.initials: RS
authors.lastname: Mann
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development* / Q000502:physiology; D029721:Drosophila Proteins; D005121:Extremities / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D017344:Genes, Insect; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D007150:Immunohistochemistry; D019476:Insect Proteins / Q000235:genetics / Q000502:physiology; D018613:Microscopy, Confocal; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D051155:Wnt1 Protein
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D019476:Insect Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D051155:Wnt1 Protein; C064196:dpp protein, Drosophila; C083405:exd protein, Drosophila; C108704:hth protein, Drosophila; C074622:wg protein, Drosophila