A gene regulatory network directed by zebrafish No tail accounts for its roles in mesoderm formation

doi:10.1073/pnas.0808382106

A gene regulatory network directed by zebrafish No tail accounts for its roles in mesoderm formation

^aDepartment of Physiology, Development and Neuroscience, Cambridge University, Anatomy Building, Downing Street, Cambridge, CB2 3DY, United Kingdom;
^bWellcome Trust/Cancer Research UK Gurdon Institute; and
^dDepartment of Zoology, Tennis Court Road, Cambridge University, Cambridge, CB2 1QN, United Kingdom; and
^cEuropean Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom

Edited by Michael S. Levine, University of California, Berkeley, CA, and approved January 8, 2009
↵¹These authors contributed equally to this work. (received for review August 24, 2008)

Abstract

Using chromatin immunoprecipitation combined with genomic microarrays we have identified targets of No tail (Ntl), a zebrafish Brachyury ortholog that plays a central role in mesoderm formation. We show that Ntl regulates a downstream network of other transcription factors and identify an in vivo Ntl binding site that resembles the consensus T-box binding site (TBS) previously identified by in vitro studies. We show that the notochord-expressed gene floating head (flh) is a direct transcriptional target of Ntl and that a combination of TBSs in the flh upstream region are required for Ntl-directed expression. Using our genome-scale data we have assembled a preliminary gene regulatory network that begins to describe mesoderm formation and patterning in the early zebrafish embryo.

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Footnotes

²To whom correspondence should be addressed. E-mail: fcw27{at}cam.ac.uk
Author contributions: J.S. and F.C.W. designed research; R.H.M., K.L., and F.C.W. performed research; D.K., M.J.G., P.F., and F.C.W. analyzed data; and D.K., P.F., J.S., and F.C.W. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: The data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE12331).
This article contains supporting information online at www.pnas.org/cgi/content/full/0808382106/DCSupplemental.