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Molecular and Cellular Biology, November 2007, p. 7497-7510, Vol. 27, No. 21
0270-7306/07/$08.00+0     doi:10.1128/MCB.00687-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Conditional Deletion of Activating Protein 2 (AP-2) in the Developing Retina Demonstrates Non-Cell-Autonomous Roles for AP-2 in Optic Cup Development

Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada,¹ Departments of CFB and CDB, University of Colorado Health Sciences Center, Denver, Colorado,² The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California,³ McKnight Vision Research Center, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida⁴

Received 19 April 2007/ Returned for modification 14 June 2007/ Accepted 14 August 2007

Activating protein 2 (AP-2) is known to be expressed in the retina, and AP-2-null mice exhibit defects in the developing optic cup, including patterning of the neural retina (NR) and a replacement of the dorsal retinal pigmented epithelium (RPE) with NR. In this study, we analyzed the temporal and spatial retinal expression patterns of AP-2 and created a conditional deletion of AP-2 in the developing retina. AP-2 exhibited a distinct expression pattern in the developing inner nuclear layer of the retina, and colocalization studies indicated that AP-2 was exclusively expressed in postmitotic amacrine cell populations. Targeted deletion of AP-2 in the developing retina did not result in observable retinal defects. Further examination of AP-2-null mutants revealed that the severity of the RPE defect was variable and, although defects in retinal lamination occur at later embryonic stages, earlier stages showed normal lamination and expression of markers for amacrine and ganglion cells. Together, these data demonstrate that, whereas AP-2 alone does not play an intrinsic role in retinogenesis, it has non-cell-autonomous effects on optic cup development. Additional expression analyses showed that multiple AP-2 proteins are present in the developing retina, which will be important to future studies.

Published ahead of print on 27 August 2007.

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