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First published online October 23, 2009
doi: 10.1242/10.1242/dev.033449


Development 136, 3767-3777 (2009)
Published by The Company of Biologists 2009


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Conserved regulatory sequences in Atoh7 mediate non-conserved regulatory responses in retina ontogenesis

Dorota Skowronska-Krawczyk1,{dagger},{ddagger},*, Florence Chiodini2,{ddagger}, Martin Ebeling3, Christine Alliod1, Adam Kundzewicz1,2, Diogo Castro4, Marc Ballivet1, François Guillemot4, Lidia Matter-Sadzinski1,2 and Jean-Marc Matter1,2,*

1 Department of Biochemistry, Sciences II, University of Geneva, 1211 Genève 4, Switzerland.
2 Department of Ophthalmology, School of Medicine, University of Geneva, 1211 Genève 4, Switzerland.
3 Bioinformatics, F. Hoffmann-La Roche, Basel 4070, Switzerland.
4 Division of Molecular Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.

* Authors for correspondence (dkrawczyk{at}ucsd.edu; Jean-Marc.Matter{at}unige.ch)

Accepted 10 September 2009

The characterisation of interspecies differences in gene regulation is crucial to understanding the molecular basis of phenotypic diversity and evolution. The atonal homologue Atoh7 participates in the ontogenesis of the vertebrate retina. Our study reveals how evolutionarily conserved, non-coding DNA sequences mediate both the conserved and the species-specific transcriptional features of the Atoh7 gene. In the mouse and chick retina, species-related variations in the chromatin-binding profiles of bHLH transcription factors correlate with distinct features of the Atoh7 promoters and underlie variations in the transcriptional rates of the Atoh7 genes. The different expression kinetics of the Atoh7 genes generate differences in the expression patterns of a set of genes that are regulated by Atoh7 in a dose-dependent manner, including those involved in neurite outgrowth and growth cone migration. In summary, we show how highly conserved regulatory elements are put to use in mediating non-conserved functions and creating interspecies neuronal diversity.

Key words: Ath5, Neurogenin 2, Trans-acting environment, Chicken, Mouse, Retinal ganglion cells


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