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doi: 10.1242/10.1242/dev.00450


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Development 130, 2903-2915 (2003)
Copyright © 2003 The Company of Biologists Limited

Retinal pigmented epithelium determination requires the redundant activities of Pax2 and Pax6

Nicole Bäumer1, Till Marquardt1,*, Anastassia Stoykova1, Derek Spieler2, Dieter Treichel1, Ruth Ashery-Padan1,{dagger} and Peter Gruss1,{ddagger}

1 Department of Molecular Cell Biology, Max-Planck-Institute of Biophysical Chemistry, Am Fassberg 11, D-37077 Göttingen, Germany
2 Department of Developmental Biology, Max-Planck-Institute of Biophysical Chemistry, Am Fassberg 11, D-37077 Göttingen, Germany
* Present address: The Salk Institute for Biological Studies, Gene Expression Laboratory, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
{dagger} Present address: Sackler Faculty of Medicine, Department of Human Genetics and Molecular Medicine, Tel Aviv University, Ramat Aviv 69978, Tel Aviv, Israel

{ddagger} Author for correspondence (e-mail: peter.gruss{at}mpg-gv.mpg.de)

Accepted 12 February 2003

The transcription factors Pax2 and Pax6 are co-expressed in the entire optic vesicle (OV) prior and concomitant with the establishment of distinct neuroretinal, retinal, pigmented-epithelial and optic-stalk progenitor domains, suggesting redundant functions during retinal determination. Pax2; Pax6 compound mutants display a dose-dependent reduction in the expression of the melanocyte determinant Mitf, accompanied by transdifferentiation of retinal pigmented epithelium (RPE) into neuroretina (NR) in Pax2-/-; Pax6+/- embryos, which strongly resembles the phenotype of Mitf-null mutants. In Pax2-/-; Pax6-/- OVs Mitf fails to be expressed and NR markers occupy the area that usually represents the Mitf+ RPE domain. Furthermore, both, Pax2 and Pax6 bind to and activate a MITF RPE-promoter element in vitro, whereas prolonged expression of Pax6 in the Pax2-positive optic stalk leads to ectopic Mitf expression and RPE differentiation in vivo. Together, these results demonstrate that the redundant activities of Pax2 and Pax6 direct the determination of RPE, potentially by directly controlling the expression of RPE determinants.

Key words: Eye development, Pigmented retina, Regionalization, Pax2, Pax6, Mitf


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