Ectopic expression of transcription factor AP-2δ in developing retina: effect on PSA-NCAM and axon routing

J Neurochem. 2014 Apr;129(1):72-84. doi: 10.1111/jnc.12521. Epub 2013 Nov 26.

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.

Keywords: AP-2delta; GAP43; PSA-NCAM; axon bundling; retinal ganglion cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology*
  • Chick Embryo
  • Chickens
  • Choristoma*
  • Gene Expression Regulation, Developmental*
  • Glycoside Hydrolases / pharmacology
  • Neural Cell Adhesion Molecule L1 / antagonists & inhibitors
  • Neural Cell Adhesion Molecule L1 / biosynthesis*
  • Retina / drug effects
  • Retina / embryology*
  • Retina / metabolism*
  • Sialic Acids / antagonists & inhibitors
  • Sialic Acids / biosynthesis*
  • Transcription Factor AP-2 / antagonists & inhibitors
  • Transcription Factor AP-2 / biosynthesis*

Substances

  • Neural Cell Adhesion Molecule L1
  • Sialic Acids
  • Transcription Factor AP-2
  • polysialyl neural cell adhesion molecule
  • Glycoside Hydrolases
  • endo-alpha-sialidase