title: The Drosophila LIM-homeo domain protein Islet antagonizes pro-neural cell specification in the peripheral nervous system.
abstract: The pattern of the external sensory organs (SO) in Drosophila depends on the activity of the basic helix-loop-helix (bHLH) transcriptional activators Achaete/Scute (Ac/Sc) that are expressed in clusters of cells (pro-neural clusters) and provide the cells with the potential to develop a neural fate. In the mesothorax, the GATA1 transcription factor Pannier (Pnr), together with its cofactor Chip, activates ac/sc genes directly through binding to the dorso-central enhancer (DC) of ac/sc. We identify the LIM-homeo domain (LIM-HD) transcription factor Islet (Isl) by genetic screening and investigate its role in the thoracic pre-patterning. We show that isl loss-of-function mutations result in expanded Ac expression in DC and scutellar (SC) pro-neural clusters and formation of ectopic sensory organs. Overexpression of Isl decreases pro-neural expression and suppresses bristle development. Moreover, Isl is coexpressed with Pnr in the posterior region of the mesothorax. In the DC pro-neural cluster, Isl antagonizes Pnr activity both by dimerization with the DNA-binding domain of Pnr and via competitive inhibition of the Chip-bHLH interaction. We propose that sensory organ pre-patterning relies on the antagonistic activity of individual Chip-binding factors. The differential affinities of these binding-factors and their precise stoichiometry are crucial in specifying pre-patterns within the different pro-neural clusters.
authors.affiliation: Department of Developmental Biology/IGBMC, 1, rue Laurent Fries, BP 10142, 67404 Illkirch CEDEX, France.
authors.forename: Inna
authors.initials: I
authors.lastname: Biryukova
authors.forename: Pascal
authors.initials: P
authors.lastname: Heitzler
mesh_terms: D000818:Animals; D019521:Body Patterning; D002454:Cell Differentiation; D019281:Dimerization; D004330:Drosophila / Q000166:cytology* / Q000235:genetics / Q000254:growth & development; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D007814:Larva; D009154:Mutation; D009420:Nervous System / Q000166:cytology / Q000254:growth & development; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011679:Pupa; D012679:Sense Organs / Q000254:growth & development / Q000294:innervation / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C108740:Chi protein, Drosophila; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C109259:pnr protein, Drosophila; C494337:tup protein, Drosophila