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Series GSE5141 Query DataSets for GSE5141
Status Public on Sep 01, 2006
Title Hex acts with β-catenin to regulate anterior-posterior
Organism Mus musculus
Experiment type Expression profiling by array
Summary In Xenopus, establishment of the anterior-posterior axis involves two key signalling pathways, canonical Wnt and Nodal-related TGF-β. There are also a number of transcription factors that feedback upon these pathways. The homeodomain protein Hex, an early marker of anterior positional information, acts as a transcriptional repressor suppressing induction and propagation of the Spemman organiser while specifying anterior identity. We show that Hex promotes anterior identity by amplifying the activity of canonical Wnt signalling. Hex exerts this activity by inhibiting the expression of Tle-4, a member of the Groucho family of transcriptional co-repressors that we identified as a Hex target in embryonic stem (ES) cells and Xenopus embryos. This Hex-mediated enhancement of Wnt signalling results in the up-regulation of the Nieuwkoop centre genes Siamois and Xnr-3 and the subsequent increased expression of the anterior endodermal marker Cerberus and other mesendodermal genes downstream of Wnt signalling. We also identified Nodal as a Hex target in ES cells. We demonstrate that in Xenopus, the Nodal-related genes Xnr-1 and 2, but not 5 and 6, are regulated directly by Hex. The identification of Nodal-related genes as Hex targets explains the ability of Hex to suppress induction and propagation of the organiser. Together these results support a model in which Hex acts early in development to reinforce a Wnt-mediated, Nieuwkoop-like signal to induce anterior endoderm, and later in this tissue to block further propagation of Nodal-related signals. The ability of Hex to regulate the same targets in both Xenopus and mouse implies this model is conserved.
Keywords: genetic modification
 
Overall design Identification of Hex target genes In Xenopus, the establishment of the anterior-posterior axis involves two key signalling pathways, the canonical Wnt and the Nodal-related TGF-β and a number of transcription factors that feedback upon these pathways. The homeodomain protein Hex, an early marker of anterior positional information, is a transcriptional repressor that suppresses the induction and propagation of the Spemman organiser while specifying anterior identity. Using microarray expression profiling we identified mouse Tle-4 as a Hex target in Embryonic Stem (ES) cells and showed that Tle-4 expression is directly regulated by Hex in Xenopus embryos. We also identified Nodal as a Hex target in ES cells. Taken together these results support a model in which Hex acts early in development to reinforce a Wnt-mediated, Nieuwkoop-like signal to induce anterior endoderm and later in this tissue to block further propagation of Nodal-related signals. The ability of Hex to regulate the same targets in both frog and mouse suggests that this model is conserved.
 
Contributor(s) Zamparini1 AL, Watts T, Gardner CE, Tomlinson SR, Johnston G, Brickman JM
Citation(s) 16936074
Submission date Jun 23, 2006
Last update date Feb 18, 2018
Contact name Joshua M Brickman
E-mail(s) Josh.Brickman@ed.ac.uk
Phone 0131-650-5866
URL http://www.iscr.ed.ac.uk/research/research-groups-josh-brickman.html
Organization name University of Edinburgh
Department Institute for Stem Cell Research
Street address King's Buildings, West Mains Rd.
City Edinburgh
ZIP/Postal code EH9 3JQ
Country United Kingdom
 
Platforms (1)
GPL81 [MG_U74Av2] Affymetrix Murine Genome U74A Version 2 Array
Samples (44)
GSM116033 Hex targetted to Rosa26, unrecombined RH_1
GSM116034 Hex targetted to Rosa26, unrecombined RH_2
GSM116035 Hex targetted to Rosa26, unrecombined RH_3
Relations
BioProject PRJNA96653

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