title: Ectopic expression of transcription factor AP-2δ in developing retina: effect on PSA-NCAM and axon routing.
abstract: Retinal ganglion cells transmit the visual signal from the retina to the brain. We have previously shown that the activator protein 2 (AP-2)δ (TFAP2D) transcription factor is expressed in one third of ganglion cells in developing retina suggesting a specialized role for these AP-2δ-expressing cells. Here, we address the role of AP-2δ in retina by in ovo electroporation of RCAS/AP-2δ retroviral constructs into the eyes of chick embryos at day 2 of gestation. Ectopic expression of AP-2δ does not affect lineage differentiation in the developing retina. However, immunostaining of retinal tissue with markers associated with axonal growth such as growth-associated protein 43 and polysialic acid-neural cell adhesion molecule (PSA-NCAM) demonstrates axonal misrouting and abnormal axonal bundling. Treatment of AP-2δ-misexpressing retinal cell cultures with endoneuraminidase, an enzyme that removes PSA from NCAM, decreases AP-2δ-induced axonal bundling. Our data suggest a role for AP-2δ in polysialylation of NCAM, with ectopic expression of AP-2δ resulting in premature bundling of emerging axons and misrouting of axons. We propose that expression of AP-2δ in a subset of ganglion cells contributes to the fine-tuning of axonal growth in the developing retina.
authors.affiliation: Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Monckton
authors.forename: Roseline
authors.initials: R
authors.lastname: Godbout
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002642:Chick Embryo; D002645:Chickens; D002828:Choristoma; D018507:Gene Expression Regulation, Developmental; D006026:Glycoside Hydrolases / Q000494:pharmacology; D039842:Neural Cell Adhesion Molecule L1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D012160:Retina / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D012794:Sialic Acids / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D050656:Transcription Factor AP-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
chemical_list: D039842:Neural Cell Adhesion Molecule L1; D012794:Sialic Acids; D050656:Transcription Factor AP-2; C103469:polysialyl neural cell adhesion molecule; D006026:Glycoside Hydrolases; C090534:endo-alpha-sialidase
keywords: AP-2delta; GAP43; PSA-NCAM; axon bundling; retinal ganglion cells