pangolinencodes a Lef-1 homologue that acts downstream of Armadillo to transduce the Wingless signal in Drosophila

Members of the Wnt/Wingless (Wg) family of signalling proteins organize many aspects of animal development by regulating the expression of particular target genes in responding cells1–6. Recent biochemical studies7–9 indicate that the vertebrate HMG-domain proteins Lef-1 and XTcf-3 can physically interact with β-catenin, a homologue of Drosophila Armadillo (Arm), the most downstream component known in the Wnt signal transduction pathway10,11. However, these studies do not address whether the endogenous Lef/Tcf family members are required in vivo to transduce Wnt signals. Using genetic methods in Drosophila, we define a new segment polarity gene, pangolin (pan), and show that its product is required in vivo for Wg signal transduction in embryos and in developing adult tissues. In addition, we show that panencodes a Lef/Tcf homologue and provide evidence that its protein product binds to the β-catenin homologue Armadillo in vivo. Finally, we demonstrate that Pan functions downstream of Arm to transduce the Wg signal. Thus, our results indicate that Pan is an essential component of the Wg transduction pathway and suggest that it acts directly to regulate gene transcription in response to Wg signalling.

[1]  M. Peifer,et al.  The segment polarity gene armadillo encodes a functionally modular protein that is the Drosophila homolog of human plakoglobin , 1990, Cell.

[2]  C. K. Motzny,et al.  The Drosophila cubitus interruptus protein and its role in the wingless and hedgehog signal transduction pathways , 1995, Mechanisms of Development.

[3]  Konrad Basler,et al.  Sending and Receiving the Hedgehog Signal: Control by the Drosophila Gli Protein Cubitus interruptus , 1996, Science.

[4]  B. Hochman Analysis of chromosome 4 in Drosophila melanogaster. II. Ethyl methanesulfonate induced lethals. , 1971, Genetics.

[5]  B. Herrmann,et al.  Nuclear localization of β-catenin by interaction with transcription factor LEF-1 , 1996, Mechanisms of Development.

[6]  G. Struhl,et al.  Direct and Long-Range Action of a Wingless Morphogen Gradient , 1996, Cell.

[7]  Konrad Basler,et al.  Organizing activity of wingless protein in Drosophila , 1993, Cell.

[8]  D. Slusarski,et al.  Mutations that alter the timing and pattern of cubitus interruptus gene expression in Drosophila melanogaster. , 1995, Genetics.

[9]  R. Lin,et al.  pop-1 Encodes an HMG box protein required for the specification of a mesoderm precursor in Early C. elegans embryos , 1995, Cell.

[10]  Michael Kühl,et al.  Functional interaction of β-catenin with the transcription factor LEF-1 , 1996, Nature.

[11]  Hans Clevers,et al.  XTcf-3 Transcription Factor Mediates β-Catenin-Induced Axis Formation in Xenopus Embryos , 1996, Cell.

[12]  N. Baker Transcription of the segment-polarity gene wingless in the imaginal discs of Drosophila, and the phenotype of a pupal-lethal wg mutation. , 1988, Development.

[13]  S. Cohen,et al.  Specification of the wing by localized expression of wingless protein , 1996, Nature.

[14]  A. Martinez Arias,et al.  Roles of wingless in patterning the larval epidermis of Drosophila. , 1991, Development.

[15]  R Grosschedl,et al.  LEF-1, a gene encoding a lymphoid-specific protein with an HMG domain, regulates T-cell receptor alpha enhancer function [corrected]. , 1991, Genes & development.

[16]  P. Lawrence,et al.  The consequences of ubiquitous expression of the wingless gene in the Drosophila embryo. , 1992, Development.

[17]  M. Bienz,et al.  decapentaplegic, a target gene of the wingless signalling pathway in the Drosophila midgut. , 1996, Development.

[18]  P. Lawrence,et al.  The development of wingless, a homeotic mutation of Drosophila. , 1977, Developmental biology.

[19]  S. Blair,et al.  Notch regulates wingless expression and is not required for reception of the paracrine wingless signal during wing margin neurogenesis in Drosophila. , 1995, Development.

[20]  E. Wieschaus,et al.  The segment polarity gene armadillo interacts with the wingless signaling pathway in both embryonic and adult pattern formation. , 1991, Development.

[21]  P. Ingham,et al.  Genetic analysis of hedgehog signalling in the Drosophila embryo. , 1993, Development (Cambridge, England). Supplement.

[22]  R. Nusse,et al.  wingless signaling in the Drosophila eye and embryonic epidermis. , 1996, Development.

[23]  Andrew P. McMahon,et al.  Engrailed-1 as a target of the Wnt-1 signalling pathway in vertebrate midbrain development , 1996, Nature.

[24]  M. Noll,et al.  Role of the gooseberry gene in Drosophila embryos: maintenance of wingless expression by a wingless‐‐gooseberry autoregulatory loop. , 1993, The EMBO journal.

[25]  P. Ingham,et al.  Transcriptional activation of hedgehog target genes in Drosophila is mediated directly by the cubitus interruptus protein, a member of the GLI family of zinc finger DNA-binding proteins. , 1996, Genes & development.

[26]  E. Hafen,et al.  Ligand-independent activation of the sevenless receptor tyrosine kinase changes the fate of cells in the developing Drosophila eye , 1991, Cell.

[27]  J. Whittle,et al.  wingless expression mediates determination of peripheral nervous system elements in late stages of Drosophila wing disc development. , 1993, Development.

[28]  A. M. Arias,et al.  The wingless signalling pathway and the patterning of the wing margin in Drosophila. , 1994, Development.

[29]  J. Couso,et al.  Cell fates in the adult abdomen of Drosophila are determined by wingless during pupal development. , 1996, Developmental biology.

[30]  F. Díaz-Benjumea,et al.  Serrate signals through Notch to establish a Wingless-dependent organizer at the dorsal/ventral compartment boundary of the Drosophila wing. , 1995, Development.

[31]  N. Perrimon,et al.  Drosophila wingless: A paradigm for the function and mechanism of Wnt signaling , 1994, BioEssays : news and reviews in molecular, cellular and developmental biology.

[32]  W. Brook,et al.  Antagonistic Interactions Between Wingless and Decapentaplegic Responsible for Dorsal-Ventral Pattern in the Drosophila Leg , 1996, Science.