Abstract
BackgroundAP-2δ is the most divergent member of the Activating Protein-2 (TFAP2) family of transcription factors. AP-2δ 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.ResultsAP-2δ knockout results in loss of Brn3c (Pou4f3) expression in AP-2δ -positive RGCs. While AP-2δ-/- 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-2δ 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-2δ-/- mice. In agreement with anatomical data, visually evoked responses recorded from the brain confirmed that retinal outputs to the brain are compromised.ConclusionsAP-2δ is important for the maintenance of ganglion cell numbers in the retina. Loss of AP-2δ 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-016-0244-0) contains supplementary material, which is available to authorized users.
Highlights
AP-2δ is the most divergent member of the Activating Protein-2 (TFAP2) family of transcription factors
AP-2δ co-localized with Brn3a-positive retinal ganglion cell (RGC) in the ganglion cell layer from E16.5 to adult, with all AP-2δ-positive cells co-immunostaining with Brn3a in P1 (125/125 cells, with counts compiled from 4 different tissue sections), P16 (158/158 cells – 8 different tissue sections) and adult retina (74/74 cells – 9 different tissue sections) (Fig. 2)
Our data demonstrate that loss of AP-2δ function during development can have phenotypically profound consequences as well as more subtle consequences
Summary
AP-2δ is the most divergent member of the Activating Protein-2 (TFAP2) family of transcription factors. AP-2δ is restricted to specific regions of the CNS, including a subset of ganglion cells in the retina. AP-2s are a family of five transcription factors (AP-2α, β, γ, δ and ε) that function as homo- or heterodimers. AP-2α, AP-2β and AP-2γ are the most widely expressed and best-characterized of the five AP-2 transcription factors, with all three AP-2s implicated in neural crest formation [1,2,3,4]. AP-2δ is the most divergent member of the AP-2 family [16] and is primarily found in heart as well as subsets of cells in the CNS [17, 18]. The inferior colliculus is the main nucleus of the auditory pathway in midbrain, AP-2δ−/− mice still respond to sound, suggesting compensation through a different auditory route
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