title: The bHLH-PAS transcription factor dysfusion regulates tarsal joint formation in response to Notch activity during drosophila leg development.
abstract: A characteristic of all arthropods is the presence of flexible structures called joints that connect all leg segments. Drosophila legs include two types of joints: the proximal or "true" joints that are motile due to the presence of muscle attachment and the distal joints that lack musculature. These joints are not only morphologically, functionally and evolutionarily different, but also the morphogenetic program that forms them is distinct. Development of both proximal and distal joints requires Notch activity; however, it is still unknown how this pathway can control the development of such homologous although distinct structures. Here we show that the bHLH-PAS transcription factor encoded by the gene dysfusion (dys), is expressed and absolutely required for tarsal joint development while it is dispensable for proximal joints. In the presumptive tarsal joints, Dys regulates the expression of the pro-apoptotic genes reaper and head involution defective and the expression of the RhoGTPases modulators, RhoGEf2 and RhoGap71E, thus directing key morphogenetic events required for tarsal joint development. When ectopically expressed, dys is able to induce some aspects of the morphogenetic program necessary for distal joint development such as fold formation and programmed cell death. This novel Dys function depends on its obligated partner Tango to activate the transcription of target genes. We also identified a dedicated dys cis-regulatory module that regulates dys expression in the tarsal presumptive leg joints through direct Su(H) binding. All these data place dys as a key player downstream of Notch, directing distal versus proximal joint morphogenesis.
authors.affiliation: Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid (UAM), Madrid, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Córdoba
authors.affiliation: Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid (UAM), Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Estella
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D005121:Extremities / Q000254:growth & development* / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D007814:Larva / Q000235:genetics / Q000254:growth & development; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013640:Tarsal Joints / Q000254:growth & development*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D009479:Neuropeptides; D051880:Receptors, Notch; D012097:Repressor Proteins; D020741:rho GTP-Binding Proteins; C108880:HID protein, Drosophila; C497759:N protein, Drosophila; C088731:Su(H) protein, Drosophila; C513659:dysf protein, Drosophila; C086973:rpr protein, Drosophila; C465504:sav protein, Drosophila; C109766:tgo protein, Drosophila