title: The Drosophila COMPASS-like Cmi-Trr coactivator complex regulates dpp/BMP signaling in pattern formation.
abstract: Drosophila Cara Mitad (Cmi, also known as Lpt) is the N-terminal homolog of mammalian Mixed Lineage Leukemia 2 (MLL2/ALR), a core component of COMPASS-like nuclear receptor coactivator complexes. Cmi is required for the activation of ecdysone hormone targets and plays a critical role in development and tissue patterning. Using multiple approaches that include genetic interaction tests and tissue specific knockdown and overexpression of cmi, we demonstrate that Cmi has important functions in controlling wing vein patterning through regulation of the conserved Decapentaplegic (Dpp) signaling pathway. The loss of function allele, cmi(1), enhances loss of dpp function phenotypes in genetic epistasis tests. Wing specific knockdown of cmi results in incomplete veins towards the distal wing margin that are enhanced by the simultaneous knockdown of dpp. In contrast, the overexpression of a tagged full-length HA-cmi transgene results in ectopic veins that are sensitive to Dpp levels. The knockdown and overexpression of cmi result in reduced and increased Dpp signaling as observed by immunostaining for phospho-MAD (Mother against DPP), a downstream effector of Dpp function. shRNAi depletion of cmi suppresses a tkv reduced function phenotype while the overexpression of HA-cmi enhances tkv RNAi phenotypes. We further show by enhancer reporter assays and chromatin immunoprecipitation that Cmi controls wing vein patterning by regulating dpp transcription directly or indirectly through the 3' disc regulatory region at the larval stage and through the 5' shortvein (shv) regulatory region at the pupal stage. Our data reveals that Cmi is a key part of the mechanism that controls wing vein patterning through nuclear receptor regulation of the Dpp signaling pathway.
authors.affiliation: Graduate Program in Molecular Biology, Stritch School of Medicine, Loyola University of Chicago Maywood IL USA.
authors.forename: Chhavi
authors.initials: C
authors.lastname: Chauhan
authors.forename: Claudia B
authors.initials: CB
authors.lastname: Zraly
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Dingwall
mesh_terms: D000818:Animals; D019521:Body Patterning; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D053823:Hedgehog Proteins / Q000235:genetics; D011495:Histone-Lysine N-Methyltransferase / Q000502:physiology*; D056918:Nuclear Receptor Coactivators / Q000502:physiology*; D015398:Signal Transduction; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000502:physiology; D014921:Wings, Animal / Q000196:embryology
chemical_list: D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; C573668:Lpt protein, Drosophila; D056918:Nuclear Receptor Coactivators; D016212:Transforming Growth Factor beta; C064196:dpp protein, Drosophila; C077245:hh protein, Drosophila; D011495:Histone-Lysine N-Methyltransferase; C479519:TRR protein, Drosophila
keywords: COMPASS-complex; Chromatin; Coactivator; Decapentaplegic; Receptor signaling; Wing development