Hox genes control vertebrate body elongation by collinear Wnt repression
Nicolas Denans,
Tadahiro Iimura,
Olivier Pourquié
Affiliations
Nicolas Denans
Institut de Génétique et de Biologie Moléculaire et Cellulaire, University of Strasbourg, Illkirch, France; Stowers Institute for Medical Research, Kansas City, United States
Tadahiro Iimura
Stowers Institute for Medical Research, Kansas City, United States; Division of Bio-Imaging Proteo-Science Center, Ehime University, Ehime, Japan
Olivier Pourquié
Institut de Génétique et de Biologie Moléculaire et Cellulaire, University of Strasbourg, Illkirch, France; Stowers Institute for Medical Research, Kansas City, United States; Howard Hughes Medical Institute, Kansas City, United States; Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, United States; Department of Pathology, Brigham and Woman's Hospital, Boston, United States; Department of Genetics, Harvard Medical School, Boston, United States
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.
