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

• Published in: Journal of neurochemistry Vol. 129; no. 1; pp. 72 - 84
• Main Authors: Li, Xiaodong, Monckton, Elizabeth A., Godbout, Roseline
• Format: Journal Article
• Language: English
• Published: England 01.04.2014
• Subjects: Animals; AP‐2delta; axon bundling; Axons - physiology; Chick Embryo; Chickens; Choristoma; GAP43; Gene Expression Regulation, Developmental; Glycoside Hydrolases - pharmacology; Neural Cell Adhesion Molecule L1 - antagonists & inhibitors; Neural Cell Adhesion Molecule L1 - biosynthesis; PSA‐NCAM; Retina - drug effects; Retina - embryology; Retina - metabolism; retinal ganglion cells; Sialic Acids - antagonists & inhibitors; Sialic Acids - biosynthesis; Transcription Factor AP-2 - antagonists & inhibitors; Transcription Factor AP-2 - biosynthesis; GAP43; retinal ganglion cells; PSA-NCAM; AP-2delta; axon bundling
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.12521

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. AP‐2δ is a transcription factor expressed in one third of retinal ganglion cells. Chick embryonic retinas which have been in ovo electroporated with a RCAS GFP‐AP‐2δ expression construct show axonal abnormalities. We propose a model whereby GFP‐AP‐2δ‐positive (green) non‐ganglion cells produce substrate or signaling molecules (e.g., PSA‐NCAM; indicated by asterisks) that cause misrouting and increased bundling of ganglion cell axons. AP‐2δ is a transcription factor expressed in one third of retinal ganglion cells. Chick embryonic retinas which have been in ovo electroporated with a RCAS GFP‐AP‐2δ expression construct show axonal abnormalities. We propose a model whereby GFP‐AP‐2δ‐positive (green) non‐ganglion cells produce substrate or signaling molecules (e.g., PSA‐NCAM; indicated by asterisks) that cause misrouting and increased bundling of ganglion cell axons.