title: Inhibition of the Pim1 oncogene results in diminished visual function.
abstract: Our objective was to profile genetic pathways whose differential expression correlates with maturation of visual function in zebrafish. Bioinformatic analysis of transcriptomic data revealed Jak-Stat signalling as the pathway most enriched in the eye, as visual function develops. Real-time PCR, western blotting, immunohistochemistry and in situ hybridization data confirm that multiple Jak-Stat pathway genes are up-regulated in the zebrafish eye between 3-5 days post-fertilisation, times associated with significant maturation of vision. One of the most up-regulated Jak-Stat genes is the proto-oncogene Pim1 kinase, previously associated with haematological malignancies and cancer. Loss of function experiments using Pim1 morpholinos or Pim1 inhibitors result in significant diminishment of visual behaviour and function. In summary, we have identified that enhanced expression of Jak-Stat pathway genes correlates with maturation of visual function and that the Pim1 oncogene is required for normal visual function.
authors.affiliation: UCD School of Medicine and Medical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland.
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.forename: Lisa
authors.initials: L
authors.lastname: Shine
authors.forename: Francis
authors.initials: F
authors.lastname: Raycroft
authors.forename: Sudhakar
authors.initials: S
authors.lastname: Deeti
authors.forename: Alison
authors.initials: A
authors.lastname: Reynolds
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Ackerman
authors.forename: Antonino
authors.initials: A
authors.lastname: Glaviano
authors.forename: Sean
authors.initials: S
authors.lastname: O'Farrell
authors.forename: Olivia
authors.initials: O
authors.lastname: O'Leary
authors.forename: Claire
authors.initials: C
authors.lastname: Kilty
authors.forename: Ciaran
authors.initials: C
authors.lastname: Kennedy
authors.forename: Sarah
authors.initials: S
authors.lastname: McLoughlin
authors.forename: Megan
authors.initials: M
authors.lastname: Rice
authors.forename: Eileen
authors.initials: E
authors.lastname: Russell
authors.forename: Desmond G
authors.initials: DG
authors.lastname: Higgins
authors.forename: David R
authors.initials: DR
authors.lastname: Hyde
authors.forename: Breandan N
authors.initials: BN
authors.lastname: Kennedy
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004596:Electroretinography; D018507:Gene Expression Regulation, Developmental; D007814:Larva / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D060172:Morpholinos / Q000494:pharmacology*; D010802:Phylogeny; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D014786:Vision Disorders / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D060172:Morpholinos; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D029961:Zebrafish Proteins; C540939:socs1a protein, zebrafish; C540940:socs3a protein, zebrafish; D051573:Proto-Oncogene Proteins c-pim-1