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

• Published in: Journal of neurochemistry Vol. 129; no. 1; p. 72
• Main Authors: Li, Xiaodong, Monckton, Elizabeth A, Godbout, Roseline
• Format: Journal Article
• Language: English
• Published: New York Blackwell Publishing Ltd 01.04.2014
• Subjects: Cell adhesion & migration; Cell culture; Neurochemistry; Retina
• 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)[delta] (TFAP2D) transcription factor is expressed in one third of ganglion cells in developing retina suggesting a specialized role for these AP-2[delta]-expressing cells. Here, we address the role of AP-2[delta] in retina by in ovo electroporation of RCAS/AP-2[delta] retroviral constructs into the eyes of chick embryos at day 2 of gestation. Ectopic expression of AP-2[delta] 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-2[delta]-misexpressing retinal cell cultures with endoneuraminidase, an enzyme that removes PSA from NCAM, decreases AP-2[delta]-induced axonal bundling. Our data suggest a role for AP-2[delta] in polysialylation of NCAM, with ectopic expression of AP-2[delta] resulting in premature bundling of emerging axons and misrouting of axons. We propose that expression of AP-2[delta] in a subset of ganglion cells contributes to the fine-tuning of axonal growth in the developing retina. AP-2[delta] 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-2[delta] expression construct show axonal abnormalities. We propose a model whereby GFP-AP-2[delta]-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. [PUBLICATION ABSTRACT]