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Hox genes control vertebrate body elongation by collinear Wnt repression.

Denans N, Iimura T, Pourquié O - Elife (2015)

Bottom Line: Our data indicate that a subset of progressively more posterior Hox genes, which are collinearly activated in vertebral precursors, repress Wnt activity with increasing strength.This leads to a graded repression of the Brachyury/T transcription factor, reducing mesoderm ingression and slowing down the elongation process.Due to the continuation of somite formation, this mechanism leads to the progressive reduction of PSM size.

View Article: PubMed Central - PubMed

Affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, University of Strasbourg, Illkirch, France.

ABSTRACT
In vertebrates, the total number of vertebrae is precisely defined. Vertebrae derive from embryonic somites that are continuously produced posteriorly from the presomitic mesoderm (PSM) during body formation. We show that in the chicken embryo, activation of posterior Hox genes (paralogs 9-13) in the tail-bud correlates with the slowing down of axis elongation. Our data indicate that a subset of progressively more posterior Hox genes, which are collinearly activated in vertebral precursors, repress Wnt activity with increasing strength. This leads to a graded repression of the Brachyury/T transcription factor, reducing mesoderm ingression and slowing down the elongation process. Due to the continuation of somite formation, this mechanism leads to the progressive reduction of PSM size. This ultimately brings the retinoic acid (RA)-producing segmented region in close vicinity to the tail bud, potentially accounting for the termination of segmentation and axis elongation.

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Mentions: In mouse, a13 is the only Hox13 required for embryonicsurvival because its mutation blocks allantois growth is required for formation of theplacenta (Shaut et al, PLOS Genet, 2008). Also whereas transgenic mice overexpressingHoxa13 from the cdx2 promoter exhibit axis truncation (Young et al,Dev Cell, 2009), overexpressing Hoxd13 from the same promoter has noeffect (Jacqueline Deschamps, personal communication). We now show that the effect ofposterior Hox genes on T repression is controlled by the N-terminaldomain of posterior Hox proteins (see text and new Figure 10). While we have not mapped precisely the sequences responsible forthe effects described in this paper, there are very significant differences in theN-terminal regions of Hoxa13 and Hoxd13 that couldexplain why in the control of ingression, of elongation and of Wnt signaling, these 2proteins show different phenotypes (see alignment in Author response image 1).Author response image 1.


Hox genes control vertebrate body elongation by collinear Wnt repression.

Denans N, Iimura T, Pourquié O - Elife (2015)

© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4384752&req=5

Mentions: In mouse, a13 is the only Hox13 required for embryonicsurvival because its mutation blocks allantois growth is required for formation of theplacenta (Shaut et al, PLOS Genet, 2008). Also whereas transgenic mice overexpressingHoxa13 from the cdx2 promoter exhibit axis truncation (Young et al,Dev Cell, 2009), overexpressing Hoxd13 from the same promoter has noeffect (Jacqueline Deschamps, personal communication). We now show that the effect ofposterior Hox genes on T repression is controlled by the N-terminaldomain of posterior Hox proteins (see text and new Figure 10). While we have not mapped precisely the sequences responsible forthe effects described in this paper, there are very significant differences in theN-terminal regions of Hoxa13 and Hoxd13 that couldexplain why in the control of ingression, of elongation and of Wnt signaling, these 2proteins show different phenotypes (see alignment in Author response image 1).Author response image 1.

Bottom Line: Our data indicate that a subset of progressively more posterior Hox genes, which are collinearly activated in vertebral precursors, repress Wnt activity with increasing strength.This leads to a graded repression of the Brachyury/T transcription factor, reducing mesoderm ingression and slowing down the elongation process.Due to the continuation of somite formation, this mechanism leads to the progressive reduction of PSM size.

View Article: PubMed Central - PubMed

Affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, University of Strasbourg, Illkirch, France.

ABSTRACT
In vertebrates, the total number of vertebrae is precisely defined. Vertebrae derive from embryonic somites that are continuously produced posteriorly from the presomitic mesoderm (PSM) during body formation. We show that in the chicken embryo, activation of posterior Hox genes (paralogs 9-13) in the tail-bud correlates with the slowing down of axis elongation. Our data indicate that a subset of progressively more posterior Hox genes, which are collinearly activated in vertebral precursors, repress Wnt activity with increasing strength. This leads to a graded repression of the Brachyury/T transcription factor, reducing mesoderm ingression and slowing down the elongation process. Due to the continuation of somite formation, this mechanism leads to the progressive reduction of PSM size. This ultimately brings the retinoic acid (RA)-producing segmented region in close vicinity to the tail bud, potentially accounting for the termination of segmentation and axis elongation.

Show MeSH
Related in: MedlinePlus