Head formation: OTX2 regulates Dkk1 and Lhx1 activity in the anterior mesendoderm.
Identifieur interne : 003510 ( PubMed/Checkpoint ); précédent : 003509; suivant : 003511Head formation: OTX2 regulates Dkk1 and Lhx1 activity in the anterior mesendoderm.
Auteurs : Chi Kin Ip [Australie] ; Nicolas Fossat [Australie] ; Vanessa Jones [Australie] ; Thomas Lamonerie [France] ; Patrick P L. Tam [Australie]Source :
- Development (Cambridge, England) [ 1477-9129 ] ; 2014.
Descripteurs français
- KwdFr :
- Animaux, Cellules 3T3, Croisements génétiques, Facteurs de transcription (métabolisme), Facteurs de transcription Otx (physiologie), Luciferases (métabolisme), Mutation, Mésoderme (physiologie), Phénotype, Protéines et peptides de signalisation intercellulaire (métabolisme), Protéines à homéodomaine LIM (métabolisme), Régulation de l'expression des gènes au cours du développement, Souris, Tête (embryologie).
- MESH :
- embryologie : Tête.
- métabolisme : Facteurs de transcription, Luciferases, Protéines et peptides de signalisation intercellulaire, Protéines à homéodomaine LIM.
- physiologie : Facteurs de transcription Otx, Mésoderme.
- Animaux, Cellules 3T3, Croisements génétiques, Mutation, Phénotype, Régulation de l'expression des gènes au cours du développement, Souris.
English descriptors
- KwdEn :
- 3T3 Cells, Animals, Crosses, Genetic, Gene Expression Regulation, Developmental, Head (embryology), Intercellular Signaling Peptides and Proteins (metabolism), LIM-Homeodomain Proteins (metabolism), Luciferases (metabolism), Mesoderm (physiology), Mice, Mutation, Otx Transcription Factors (physiology), Phenotype, Transcription Factors (metabolism).
- MESH :
- chemical , metabolism : Intercellular Signaling Peptides and Proteins, LIM-Homeodomain Proteins, Luciferases, Transcription Factors.
- embryology : Head.
- physiology : Mesoderm, Otx Transcription Factors.
- 3T3 Cells, Animals, Crosses, Genetic, Gene Expression Regulation, Developmental, Mice, Mutation, Phenotype.
Abstract
The Otx2 gene encodes a paired-type homeobox transcription factor that is essential for the induction and the patterning of the anterior structures in the mouse embryo. Otx2 knockout embryos fail to form a head. Whereas previous studies have shown that Otx2 is required in the anterior visceral endoderm and the anterior neuroectoderm for head formation, its role in the anterior mesendoderm (AME) has not been assessed specifically. Here, we show that tissue-specific ablation of Otx2 in the AME phenocopies the truncation of the embryonic head of the Otx2 null mutant. Expression of Dkk1 and Lhx1, two genes that are also essential for head formation, is disrupted in the AME of the conditional Otx2-deficient embryos. Consistent with the fact that Dkk1 is a direct target of OTX2, we showed that OTX2 can interact with the H1 regulatory region of Dkk1 to activate its expression. Cross-species comparative analysis, RT-qPCR, ChIP-qPCR and luciferase assays have revealed two conserved regions in the Lhx1 locus to which OTX2 can bind to activate Lhx1 expression. Abnormal development of the embryonic head in Otx2;Lhx1 and Otx2;Dkk1 compound mutant embryos highlights the functional intersection of Otx2, Dkk1 and Lhx1 in the AME for head formation.
DOI: 10.1242/dev.114900
PubMed: 25231759
Affiliations:
- Australie, France
- Nouvelle-Galles du Sud, Provence-Alpes-Côte d'Azur
- Nice, Sydney
- Université Nice Sophia Antipolis, Université de Sydney
Links toward previous steps (curation, corpus...)
Links to Exploration step
pubmed:25231759Le document en format XML
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<front><div type="abstract" xml:lang="en">The Otx2 gene encodes a paired-type homeobox transcription factor that is essential for the induction and the patterning of the anterior structures in the mouse embryo. Otx2 knockout embryos fail to form a head. Whereas previous studies have shown that Otx2 is required in the anterior visceral endoderm and the anterior neuroectoderm for head formation, its role in the anterior mesendoderm (AME) has not been assessed specifically. Here, we show that tissue-specific ablation of Otx2 in the AME phenocopies the truncation of the embryonic head of the Otx2 null mutant. Expression of Dkk1 and Lhx1, two genes that are also essential for head formation, is disrupted in the AME of the conditional Otx2-deficient embryos. Consistent with the fact that Dkk1 is a direct target of OTX2, we showed that OTX2 can interact with the H1 regulatory region of Dkk1 to activate its expression. Cross-species comparative analysis, RT-qPCR, ChIP-qPCR and luciferase assays have revealed two conserved regions in the Lhx1 locus to which OTX2 can bind to activate Lhx1 expression. Abnormal development of the embryonic head in Otx2;Lhx1 and Otx2;Dkk1 compound mutant embryos highlights the functional intersection of Otx2, Dkk1 and Lhx1 in the AME for head formation.</div>
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<Abstract><AbstractText>The Otx2 gene encodes a paired-type homeobox transcription factor that is essential for the induction and the patterning of the anterior structures in the mouse embryo. Otx2 knockout embryos fail to form a head. Whereas previous studies have shown that Otx2 is required in the anterior visceral endoderm and the anterior neuroectoderm for head formation, its role in the anterior mesendoderm (AME) has not been assessed specifically. Here, we show that tissue-specific ablation of Otx2 in the AME phenocopies the truncation of the embryonic head of the Otx2 null mutant. Expression of Dkk1 and Lhx1, two genes that are also essential for head formation, is disrupted in the AME of the conditional Otx2-deficient embryos. Consistent with the fact that Dkk1 is a direct target of OTX2, we showed that OTX2 can interact with the H1 regulatory region of Dkk1 to activate its expression. Cross-species comparative analysis, RT-qPCR, ChIP-qPCR and luciferase assays have revealed two conserved regions in the Lhx1 locus to which OTX2 can bind to activate Lhx1 expression. Abnormal development of the embryonic head in Otx2;Lhx1 and Otx2;Dkk1 compound mutant embryos highlights the functional intersection of Otx2, Dkk1 and Lhx1 in the AME for head formation.</AbstractText>
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<affiliations><list><country><li>Australie</li>
<li>France</li>
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<region><li>Nouvelle-Galles du Sud</li>
<li>Provence-Alpes-Côte d'Azur</li>
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<settlement><li>Nice</li>
<li>Sydney</li>
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<orgName><li>Université Nice Sophia Antipolis</li>
<li>Université de Sydney</li>
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<tree><country name="Australie"><region name="Nouvelle-Galles du Sud"><name sortKey="Ip, Chi Kin" sort="Ip, Chi Kin" uniqKey="Ip C" first="Chi Kin" last="Ip">Chi Kin Ip</name>
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<name sortKey="Fossat, Nicolas" sort="Fossat, Nicolas" uniqKey="Fossat N" first="Nicolas" last="Fossat">Nicolas Fossat</name>
<name sortKey="Jones, Vanessa" sort="Jones, Vanessa" uniqKey="Jones V" first="Vanessa" last="Jones">Vanessa Jones</name>
<name sortKey="Tam, Patrick P L" sort="Tam, Patrick P L" uniqKey="Tam P" first="Patrick P L" last="Tam">Patrick P L. Tam</name>
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<country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Lamonerie, Thomas" sort="Lamonerie, Thomas" uniqKey="Lamonerie T" first="Thomas" last="Lamonerie">Thomas Lamonerie</name>
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