Loss of AP-2delta reduces retinal ganglion cell numbers and axonal projections to the superior colliculus.
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. Retinal ganglion cells (RGCs), the only output neurons of the retina, are responsible for transmitting the visual signal to the brain.



AP-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.



AP-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.
Department of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton, AB, T6G 1Z2, Canada.
Xiaodong
X
Li
Department of Physiology, University of Alberta, 11560 University Avenue, Edmonton, AB, Canada.|Department of Ophthalmology, University of Alberta, 11560 University Avenue, Edmonton, AB, Canada.
Frédéric
F
Gaillard
Department of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton, AB, T6G 1Z2, Canada.
Elizabeth A
EA
Monckton
Department of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton, AB, T6G 1Z2, Canada.
Darryl D
DD
Glubrecht
Department of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton, AB, T6G 1Z2, Canada.
Amit R L
AR
Persad
Max-Planck-Institute of Biochemistry, Martinsried, Germany.
Markus
M
Moser
Department of Physiology, University of Alberta, 11560 University Avenue, Edmonton, AB, Canada.|Department of Ophthalmology, University of Alberta, 11560 University Avenue, Edmonton, AB, Canada.
Yves
Y
Sauvé
Department of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton, AB, T6G 1Z2, Canada. rgodbout@ualberta.ca.
Roseline
R
Godbout
D000818:Animals; D017209:Apoptosis; D001369:Axons / Q000378:metabolism*; D002452:Cell Count; D047369:Chromatin Immunoprecipitation; D055253:Color Vision; D003623:Dark Adaptation; D005074:Evoked Potentials, Visual / Q000502:physiology; D005829:Geniculate Bodies / Q000166:cytology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000378:metabolism*; D013477:Superior Colliculi / Q000166:cytology / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000378:metabolism; D050656:Transcription Factor AP-2 / Q000172:deficiency* / Q000378:metabolism; D050821:Transcription Factor Brn-3C / Q000378:metabolism
D018398:Homeodomain Proteins; C121290:Pou4f3 protein, mouse; D050656:Transcription Factor AP-2; D050821:Transcription Factor Brn-3C
AP-2; Axon; Brain; Electrophysiology; Ganglion cells; Retina; Superior colliculus; Transcription factor