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GEO help: Mouse over screen elements for information. |
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| 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
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| 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
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| 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.
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| Contributor(s) |
Zamparini1 AL, Watts T, Gardner CE, Tomlinson SR, Johnston G, Brickman JM |
| Citation(s) |
16936074 |
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| Submission date |
Jun 23, 2006 |
| Last update date |
Feb 18, 2018 |
| Contact name |
Joshua M Brickman |
| E-mail(s) |
[email protected]
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| Phone |
0131-650-5866
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| URL |
http://www.iscr.ed.ac.uk/research/research-groups-josh-brickman.html
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| Organization name |
University of Edinburgh
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| Department |
Institute for Stem Cell Research
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| Street address |
King's Buildings, West Mains Rd.
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| City |
Edinburgh |
| ZIP/Postal code |
EH9 3JQ |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL81 |
[MG_U74Av2] Affymetrix Murine Genome U74A Version 2 Array |
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| Samples (44)
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| GSM116033 |
Hex targetted to Rosa26, unrecombined RH_1 |
| GSM116034 |
Hex targetted to Rosa26, unrecombined RH_2 |
| GSM116035 |
Hex targetted to Rosa26, unrecombined RH_3 |
| GSM116036 |
Hex targetted to Rosa26, unrecombined RH_4 |
| GSM116037 |
HexERTVP2 targetted to Rosa26, clone1, unrecombined, no 4-OHT RHETVPcl1_1 |
| GSM116038 |
HexERTVP2 targetted to Rosa26, clone1, unrecombined, no 4-OHT RHETVPcl1_2 |
| GSM116039 |
HexERTVP2 targetted to Rosa26, clone1, unrecombined, no 4-OHT RHETVPcl1_3 |
| GSM116040 |
HexERTVP2 targetted to Rosa26, clone1, unrecombined, no 4-OHT RHETVPcl1_4 |
| GSM116041 |
HexERTVP2 targetted to Rosa26, clone1, unrecombined, no 4-OHT RHETVPcl1_5 |
| GSM116042 |
HexERTVP2 targetted to Rosa26, clone1, unrecombined, 4-OHT RHETVPcl1+4-OHT_1 |
| GSM116043 |
HexERTVP2 targetted to Rosa26, clone1, unrecombined, 4-OHT RHETVPcl1+4-OHT_2 |
| GSM116044 |
HexERTVP2 targetted to Rosa26, clone2, unrecombined, 4-OHT RHETVPcl1+4-OHT_3 |
| GSM116045 |
HexERTVP2 targetted to Rosa26, clone1, unrecombined, 4-OHT RHETVPcl1+4-OHT_4 |
| GSM116046 |
HexERTVP2 targetted to Rosa26, clone2, unrecombined, no 4-OHT RHETVPcl2_1 |
| GSM116047 |
HexERTVP2 targetted to Rosa26, clone2, unrecombined, no 4-OHT RHETVPcl2_2 |
| GSM116048 |
HexERTVP2 targetted to Rosa26, clone2, unrecombined, no 4-OHT RHETVPcl2_3 |
| GSM116049 |
HexERTVP2 targetted to Rosa26, clone2, unrecombined, no 4-OHT RHETVPcl2+4-OHT_1 |
| GSM116050 |
HexERTVP2 targetted to Rosa26, clone2, unrecombined, 4-OHT RHETVPcl2+4-OHT_2 |
| GSM116051 |
HexERTVP2 targetted to Rosa26, clone2, unrecombined, 4-OHT RHETVPcl2+4-OHT_3 |
| GSM116052 |
HexERTVP2 targetted to Rosa26, clone2, unrecombined, 4-OHT RHETVPcl2+4-OHT_4 |
| GSM116053 |
Hex targetted to Rosa26, recombined RRH_1 |
| GSM116054 |
Hex targetted to Rosa26, recombined RRH_2 |
| GSM116055 |
Hex targetted to Rosa26, recombined RRH_3 |
| GSM116056 |
Hex targetted to Rosa26, recombined RRH_4 |
| GSM116057 |
HexERTVP2 targetted to Rosa26, clone1, recombined, no 4-OHT RRHETVPcl1_1 |
| GSM116058 |
HexERTVP2 targetted to Rosa26, clone1, recombined, no 4-OHT RRHETVPcl1_2 |
| GSM116059 |
HexERTVP2 targetted to Rosa26, clone1, recombined, no 4-OHT RRHETVPcl1_3 |
| GSM116060 |
HexERTVP2 targetted to Rosa26, clone1, recombined, no 4-OHT RRHETVPcl1_4 |
| GSM116061 |
HexERTVP2 targetted to Rosa26, clone1, recombined, 4-OHT RRHETVPcl1+4-OHT_1 |
| GSM116062 |
HexERTVP2 targetted to Rosa26, clone1, recombined, 4-OHT RRHETVPcl1+4-OHT_2 |
| GSM116063 |
HexERTVP2 targetted to Rosa26, clone1, recombined, 4-OHT RRHETVPcl1+4-OHT_3 |
| GSM116064 |
HexERTVP2 targetted to Rosa26, clone1, recombined, 4-OHT RRHETVPcl1+4-OHT_4 |
| GSM116065 |
HexERTVP2 targetted to Rosa26, clone1, recombined, 4-OHT RRHETVPcl2_1 |
| GSM116066 |
HexERTVP2 targetted to Rosa26, clone2, recombined, no 4-OHT RRHETVPcl2_2 |
| GSM116067 |
HexERTVP2 targetted to Rosa26, clone2, recombined, no 4-OHT RRHETVPcl2_3 |
| GSM116068 |
HexERTVP2 targetted to Rosa26, clone2, recombined, no 4-OHT RRHETVPcl2_4 |
| GSM116069 |
HexERTVP2 targetted to Rosa26, clone1, recombined, 4-OHT RRHETVPcl2+4-OHT_1 |
| GSM116070 |
HexERTVP2 targetted to Rosa26, clone2, recombined, 4-OHT RRHETVPcl2+4-OHT_2 |
| GSM116071 |
HexERTVP2 targetted to Rosa26, clone2, recombined, 4-OHT RRHETVPcl2+4-OHT_3 |
| GSM116072 |
HexERTVP2 targetted to Rosa26, clone2, recombined, 4-OHT RRHETVPcl2+-4-OHT_4 |
| GSM116073 |
CGR8.8 wild-type cells WT_1 |
| GSM116074 |
CGR8.8 wild-type cells WT_2 |
| GSM116075 |
CGR8.8 wild-type cells WT_3 |
| GSM116076 |
CGR8.8 wild-type cells WT_4 |
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| Relations |
| BioProject |
PRJNA96653 |
| Supplementary data files not provided |
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