Rapid identification of PAX2/5/8 direct downstream targets in the otic vesicle by combinatorial use of bioinformatics tools
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* Corresponding author: Joachim Wittbrodt Jochen.Wittbrodt@EMBL-heidelberg.de
1 Developmental Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117-Heidelberg, Germany
2 Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Veterinärplatz 1, A-1210 Vienna, Austria
3 European Bioinformatics Institute, Wellcome Trust Genome Campus Hinxton, Cambridge, CB10 1SD, UK
4 University of Applied Sciences FH Campus Wien, Viehmarktgasse 2A, 1030 Vienna, Austria
5 Current Address: Max-Planck Institute of Immunbiology, Stübeweg 51, 79108-Freiburg, Germany
Genome Biology 2008, 9:R145 doi:10.1186/gb-2008-9-10-r145
Published: 1 October 2008Abstract
Background
The pax2/5/8 genes belonging to the PAX family of transcription factors are key developmental regulators that are involved in the patterning of various embryonic tissues. More particularly, their function in inner ear specification has been widely described. However, little is known about the direct downstream targets and, so far, no global approaches have been performed to identify these target genes in this particular tissue.
Results
Here we present an original bioinformatics pipeline composed of comparative genomics, database querying and text mining tools, which is designed to rapidly and specifically discover PAX2/5/8 direct downstream targets involved in inner ear development. We provide evidence supported by experimental validation in medaka fish that brain 2 (POU domain, class 3, transcription factor 2), claudin-7, secretory pathway component sec31-like and meteorin-like precursor are novel direct downstream targets of PAX2/5/8.
Conclusions
This study illustrates the power of extensive mining of public data repositories using bioinformatics methods to provide answers for a specific biological question. It furthermore demonstrates how the usage of such a combinatorial approach is advantageous for the biologist in terms of experimentation time and costs.