title: Homeotic function of Drosophila Bithorax-complex miRNAs mediates fertility by restricting multiple Hox genes and TALE cofactors in the CNS.
abstract: The Drosophila Bithorax complex (BX-C) Hox cluster contains a bidirectionally transcribed miRNA locus, and a deletion mutant (Δmir) lays no eggs and is completely sterile. We show these miRNAs are expressed and active in distinct spatial registers along the anterior-posterior axis in the CNS. Δmir larvae derepress a network of direct homeobox gene targets in the posterior ventral nerve cord (VNC), including BX-C genes and their TALE cofactors. These are phenotypically critical targets, because sterility of Δmir mutants was substantially rescued by heterozygosity of these genes. The posterior VNC contains Ilp7+ oviduct motoneurons, whose innervation and morphology are defective in Δmir females, and substantially rescued by heterozygosity of Δmir targets, especially within the BX-C. Collectively, we reveal (1) critical roles for Hox miRNAs that determine segment-specific expression of homeotic genes, which are not masked by transcriptional regulation; and (2) that BX-C miRNAs are essential for neural patterning and reproductive behavior.
authors.affiliation: Department of Developmental Biology, Sloan-Kettering Institute, 1275 York Avenue, Box 252, New York, NY 10065, USA; 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: Daniel L
authors.initials: DL
authors.lastname: Garaulet
authors.affiliation: 2401 Life Sciences Centre, 2350 Health Sciences Mall, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Monica C
authors.initials: MC
authors.lastname: Castellanos
authors.affiliation: Department of Developmental Biology, Sloan-Kettering Institute, 1275 York Avenue, Box 252, New York, NY 10065, USA.
authors.forename: Fernando
authors.initials: F
authors.lastname: Bejarano
authors.affiliation: Department of Developmental Biology, Sloan-Kettering Institute, 1275 York Avenue, Box 252, New York, NY 10065, USA; Gerstner Sloan-Kettering Graduate School of Biomedical Sciences, 417 East 68th Street, New York, NY 10065, USA.
authors.forename: Piero
authors.initials: P
authors.lastname: Sanfilippo
authors.affiliation: Department of Developmental Biology, Sloan-Kettering Institute, 1275 York Avenue, Box 252, New York, NY 10065, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Tyler
authors.affiliation: 2401 Life Sciences Centre, 2350 Health Sciences Mall, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Allan
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.csic.es.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Sánchez-Herrero
authors.affiliation: Department of Developmental Biology, Sloan-Kettering Institute, 1275 York Avenue, Box 252, New York, NY 10065, USA. Electronic address: laie@mskcc.org.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Lai
mesh_terms: D000818:Animals; D001483:Base Sequence; D019521:Body Patterning; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005801:Genes, Homeobox / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics*; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D007814:Larva / Q000254:growth & development / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D005810:Multigene Family; D010057:Oviducts / Q000166:cytology / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D012726:Sexual Behavior, Animal; D014157:Transcription Factors / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D035683:MicroRNAs; D014157:Transcription Factors; C476930:achi protein, Drosophila