title: Hindsight regulates photoreceptor axon targeting through transcriptional control of jitterbug/Filamin and multiple genes involved in axon guidance in Drosophila.
abstract: During axon targeting, a stereotyped pattern of connectivity is achieved by the integration of intrinsic genetic programs and the response to extrinsic long and short-range directional cues. How this coordination occurs is the subject of intense study. Transcription factors play a central role due to their ability to regulate the expression of multiple genes required to sense and respond to these cues during development. Here we show that the transcription factor HNT regulates layer-specific photoreceptor axon targeting in Drosophila through transcriptional control of jbug/Filamin and multiple genes involved in axon guidance and cytoskeleton organization.Using a microarray analysis we identified 235 genes whose expression levels were changed by HNT overexpression in the eye primordia. We analyzed nine candidate genes involved in cytoskeleton regulation and axon guidance, six of which displayed significantly altered gene expression levels in hnt mutant retinas. Functional analysis confirmed the role of OTK/PTK7 in photoreceptor axon targeting and uncovered Tiggrin, an integrin ligand, and Jbug/Filamin, a conserved actin- binding protein, as new factors that participate of photoreceptor axon targeting. Moreover, we provided in silico and molecular evidence that supports jbug/Filamin as a direct transcriptional target of HNT and that HNT acts partially through Jbug/Filamin in vivo to regulate axon guidance. Our work broadens the understanding of how HNT regulates the coordinated expression of a group of genes to achieve the correct connectivity pattern in the Drosophila visual system. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1018-1032, 2015.
authors: Laboratorio de Neurobiología Celular y Molecular, Programa de Fisiología y Biofísica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile.|Biomedical Neurosciences Institute, ICM, Facultad de Medicina, Universidad de Chile.
authors: Carlos
authors: C
authors: Oliva
authors: Laboratorio de Genética del Desarrollo de Drosophila, Programa de Genética Humana, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile.
authors: Claudia
authors: C
authors: Molina-Fernandez
authors: Laboratorio de Genética del Desarrollo de Drosophila, Programa de Genética Humana, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile.
authors: Miguel
authors: M
authors: Maureira
authors: Laboratorio de Genética del Desarrollo de Drosophila, Programa de Genética Humana, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile.
authors: Noemi
authors: N
authors: Candia
authors: Laboratorio de Neurobiología Celular y Molecular, Programa de Fisiología y Biofísica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile.|Biomedical Neurosciences Institute, ICM, Facultad de Medicina, Universidad de Chile.
authors: Estefanía
authors: E
authors: López
authors: Laboratory of Neurogenetics, Department of Molecular and Developmental Genetics, VIB, K.U. Leuven, Leuven, Belgium.
authors: Bassem
authors: B
authors: Hassan
authors: Laboratory of Neurogenetics, Department of Molecular and Developmental Genetics, VIB, K.U. Leuven, Leuven, Belgium.
authors: Stein
authors: S
authors: Aerts
authors: Laboratorio de Neurobiología Celular y Molecular, Programa de Fisiología y Biofísica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile.|Biomedical Neurosciences Institute, ICM, Facultad de Medicina, Universidad de Chile.
authors: José
authors: J
authors: Cánovas
authors: Laboratorio de Genética del Desarrollo de Drosophila, Programa de Genética Humana, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile.
authors: Patricio
authors: P
authors: Olguín
authors: Laboratorio de Neurobiología Celular y Molecular, Programa de Fisiología y Biofísica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile.|Biomedical Neurosciences Institute, ICM, Facultad de Medicina, Universidad de Chile.
authors: Jimena
authors: J
authors: Sierralta
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D064448:Filamins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D017956:Photoreceptor Cells, Invertebrate / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D012160:Retina / Q000254:growth & development / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D016326:Extracellular Matrix Proteins; D064448:Filamins; D009687:Nuclear Proteins; C089678:Tig protein, Drosophila; D014157:Transcription Factors; C106513:peb protein, Drosophila; C494333:Otk protein, Drosophila; D020794:Receptor Protein-Tyrosine Kinases
keywords: Drosophila; Filamins; axon targeting; hindsight