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First published online March 24, 2005
doi: 10.1242/10.1242/dev.01738
1-crystallin enhancer activity in Drosophila reveals remarkable evolutionary conservation between chicken and fly
1 Department of Cell Biology, Biozentrum, University of Basel,
Klingelbergstrasse 70, CH-4056 Basel, Switzerland
2 Institut de Génétique Humaine, Centre National de la Recherche
Scientifique UPR 1142, 141 rue de la Cardonille, 34396 Montpellier,
France
3 Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka,
Suita, Osaka 565-0871, Japan
* Author for correspondence (e-mail: Walter.Gehring{at}unibas.ch)
Accepted 3 February 2005
Functional conservation of enhancers among evolutionarily diverged
organisms is a powerful way to identify basic regulatory circuits and key
developmental regulators. This is especially applicable to Crystallin genes.
Despite unexpected heterogeneity and diversity in their DNA sequences, many
studies have revealed that most of the Crystallin genes are regulated by a
relatively small set of developmentally important transcription factors. The
chicken
1-crystallin is one of the best-characterized
Crystallin genes. Its lens-specific regulation is governed by a 30 bp long DC5
fragment present in the third intron of the gene. DC5 contains PAX6 and SOX2
binding sites, and its activity depends on the cooperative binding of these
two transcription factors. To test the idea that Pax6 and
Sox2, together with the DC5 enhancer, could form a basic regulatory
circuit functional in distantly related animals, we introduced the DC5
fragment into Drosophila and studied its activation pattern and
regulation. The results show that the DC5 enhancer is not only active in the
compound eye but, remarkably, is specifically active in those cells
responsible for Crystallin secretion in Drosophila, i.e. the cone
cells. However, regulation of the DC5 enhancer is carried out not by
Pax6, but by Pax2 (D-Pax2; shaven
FlyBase) in combination with the Sox2 homologue SoxN. Both
proteins (D-PAX2 and SOXN) bind cooperatively to the DC5 fragment and activate
the enhancer synergistically. As PAX6 and PAX2 proteins derive from the same
ancestor, we propose that during evolution Pax6 function in
vertebrate lens development was retained by Pax2 in
Drosophila.
Key words: Crystallin, Enhancer conservation, Pax6, Pax2, Sox2, SoxN, Drosophila
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