title: The zinc finger homeodomain-2 gene of Drosophila controls Notch targets and regulates apoptosis in the tarsal segments.
abstract: The development of the Drosophila leg is a good model to study processes of pattern formation, cell death and segmentation. Such processes require the coordinate activity of different genes and signaling pathways that progressively subdivide the leg territory into smaller domains. One of the main pathways needed for leg development is the Notch pathway, required for determining the proximo-distal axis of the leg and for the formation of the joints that separate different leg segments. The mechanisms required to coordinate such events are largely unknown. We describe here that the zinc finger homeodomain-2 (zfh-2) gene is highly expressed in cells that will form the leg joints and needed to establish a correct size and pattern in the distal leg. There is an early requirement of zfh-2 to establish the correct proximo-distal axis, but zfh-2 is also needed at late third instar to form the joint between the fourth and fifth tarsal segments. The expression of zfh-2 requires Notch activity but zfh-2 is necessary, in turn, to activate Notch targets such as Enhancer of split and big brain. zfh-2 is controlled by the Drosophila activator protein 2 gene and regulates the late expression of tarsal-less. In the absence of zfh-2 many cells ectopically express the pro-apoptotic gene head involution defective, activate caspase-3 and are positive for acridine orange, indicating they undergo apoptosis. Our results demonstrate the key role of zfh-2 in the control of cell death and Notch signaling during leg development.
authors.affiliation: Centro de Biología Molecular Severo Ochoa (C.S.I.C.-U.A.M.), Universidad Autónoma de Madrid, Nicolás Cabrera 1, Cantoblanco, 28049 Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Guarner
authors.affiliation: Centro de Biología Molecular Severo Ochoa (C.S.I.C.-U.A.M.), Universidad Autónoma de Madrid, Nicolás Cabrera 1, Cantoblanco, 28049 Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Manjón
authors.affiliation: School of Biological Sciences, Campus Box 4120, Illinois State University Normal, IL61790-4120, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Edwards
authors.affiliation: Howard Hughes Medical Institute, The Rockefeller University, New York, USA.
authors.forename: Hermann
authors.initials: H
authors.lastname: Steller
authors.affiliation: Centro de Biología Molecular Severo Ochoa (C.S.I.C.-U.A.M.), Universidad Autónoma de Madrid, Nicolás Cabrera 1, Cantoblanco, 28049 Madrid, Spain.. Electronic address: magali.suzanne@univ-tlse3.fr.
authors.forename: Magali
authors.initials: M
authors.lastname: Suzanne
authors.affiliation: Centro de Biología Molecular Severo Ochoa (C.S.I.C.-U.A.M.), Universidad Autónoma de Madrid, Nicolás Cabrera 1, Cantoblanco, 28049 Madrid, Spain.. Electronic address: esherrero@cbm.uam.es.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Sánchez-Herrero
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics*; D018398:Homeodomain Proteins / Q000502:physiology; D051880:Receptors, Notch / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D013643:Tarsus, Animal / Q000166:cytology* / Q000254:growth & development; D014157:Transcription Factors / Q000502:physiology; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; D014157:Transcription Factors; C117261:distal-less protein, insect; C077729:Zfh2 protein, Drosophila
keywords: Apoptosis; Leg development; Notch; hid; zfh-2