Rapid identification of PAX2/5/8 direct downstream targets in the otic vesicle by combinatorial use of bioinformatics tools.
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.
Ramialison
Mirana
M
Developmental Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg, Germany.
Bajoghli
Baubak
B
Aghaallaei
Narges
N
Ettwiller
Laurence
L
Gaudan
Sylvain
S
Wittbrodt
Beate
B
Czerny
Thomas
T
Wittbrodt
Joachim
J
D000818:Animals; D019295:Computational Biology / Q000379:methods*; D057225:Data Mining; D030541:Databases, Genetic; D007758:Ear, Inner / Q000196:embryology / Q000378:metabolism*; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism; D005399:Fishes / Q000378:metabolism; D023281:Genomics; D006801:Humans; D051762:PAX2 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*
D029941:Fish Proteins; D051762:PAX2 Transcription Factor; D051757:PAX5 Transcription Factor; D051761:Paired Box Transcription Factors