The AP-2δ transcription factor is restricted to a subset of retinal ganglion cells. Overexpression of AP-2δ in chick retina results in induction of polysialylated neural cell adhesion molecule (PSA-NCAM) accompanied by misrouting and bundling of ganglion cell axons. Two polysialyltransferases, ST8SIA2 and ST8SIA4, are responsible for polysialylation of NCAM. Here, we investigate the mechanism driving the increase in PSA-NCAM observed upon AP-2δ overexpression. We show that ST8SIA2 is induced by AP-2δ overexpression in chick retina. We use chromatin immunoprecipitation and gel shift assays to demonstrate direct interaction between AP-2δ and the ST8SIA2 promoter. We propose that up-regulation of ST8SIA2 upon AP-2δ overexpression in retina increases ectopic polysialylation of NCAM which in turn causes premature bundling of axons and alters axonal response to guidance cues.