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doi: 10.1242/10.1242/dev.00450
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
Present address: Sackler Faculty of Medicine, Department of Human Genetics and
Molecular Medicine, Tel Aviv University, Ramat Aviv 69978, Tel Aviv,
Israel
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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