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Abstract

Background: AP-2 delta is the most divergent member of the Activating Protein-2 (TFAP2) family of transcription factors. AP-2 delta is restricted to specific regions of the CNS, including a subset of ganglion cells in the retina. Retinal ganglion cells (RGCs), the only output neurons of the retina, are responsible for transmitting the visual signal to the brain. Results: AP-2 delta knockout results in loss of Brn3c (Pou4f3) expression in AP-2 delta -positive RGCs. While AP-2 delta-/- mice have morphologically normal retinas at birth, there is a significant reduction in retinal ganglion cell numbers by P21, after eye opening. Chromatin immunoprecipitation indicates that Brn3c is a target of AP-2 delta in the retina. Using fluorochrome-conjugated cholera toxin subunit B to trace ganglion cell axons from the eye to the major visual pathways in the brain, we found 87 % and 32 % decreases in ipsilateral and contralateral projections, respectively, to the superior colliculus in AP-2 delta-/- mice. In agreement with anatomical data, visually evoked responses recorded from the brain confirmed that retinal outputs to the brain are compromised. Conclusions: AP-2 delta is important for the maintenance of ganglion cell numbers in the retina. Loss of AP-2 delta alters retinal axonal projections to visual centers of the brain, with ipsilaterial projections to the superior colliculus being the most dramatically affected. Our results have important implications for integration of the visual signal at the superior colliculus.