title: Roles of retinoic acid and Tbx1/10 in pharyngeal segmentation: amphioxus and the ancestral chordate condition.
abstract: BACKGROUND
  Although chordates descend from a segmented ancestor, the evolution of head segmentation has been very controversial for over 150 years. Chordates generally possess a segmented pharynx, but even though anatomical evidence and gene expression analyses suggest homologies between the pharyngeal apparatus of invertebrate chordates, such as the cephalochordate amphioxus, and vertebrates, these homologies remain contested. We, therefore, decided to study the evolution of the chordate head by examining the molecular mechanisms underlying pharyngeal morphogenesis in amphioxus, an animal lacking definitive neural crest.
  
  
  RESULTS
  Focusing on the role of retinoic acid (RA) in post-gastrulation pharyngeal morphogenesis, we found that during gastrulation, RA signaling in the endoderm is required for defining pharyngeal and non-pharyngeal domains and that this process involves active degradation of RA anteriorly in the embryo. Subsequent extension of the pharyngeal territory depends on the creation of a low RA environment and is coupled to body elongation. RA further functions in pharyngeal segmentation in a regulatory network involving the mutual inhibition of RA- and Tbx1/10-dependent signaling.
  
  
  CONCLUSIONS
  These results indicate that the involvement of RA signaling and its interactions with Tbx1/10 in head segmentation preceded the evolution of neural crest and were thus likely present in the ancestral chordate. Furthermore, developmental comparisons between different deuterostome models suggest that the genetic mechanisms for pharyngeal segmentation are evolutionary ancient and very likely predate the origin of chordates.
authors: Marine Biology Research Division, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92093-0202 USA.
authors: Demian
authors: D
authors: Koop
authors: Institut de Génomique Fonctionnelle de Lyon (CNRS UMR 5242, UCBL, ENS, INRA 1288), Ecole Normale Supérieure de Lyon, 69364 Lyon, Cedex 07, France.
authors: Jie
authors: J
authors: Chen
authors: Institut de Génomique Fonctionnelle de Lyon (CNRS UMR 5242, UCBL, ENS, INRA 1288), Ecole Normale Supérieure de Lyon, 69364 Lyon, Cedex 07, France.
authors: Maria
authors: M
authors: Theodosiou
authors: Sorbonne Universités, UPMC Université Paris 06, CNRS, UMR 7009, Laboratoire de Biologie du Développement de Villefranche-sur-Mer, Observatoire Océanologique de Villefranche-sur-Mer, 06230 Villefranche-sur-Mer, France ; CNRS, UMR 7009, Laboratoire de Biologie du Développement de Villefranche-sur-Mer, Observatoire Océanologique de Villefranche-sur-Mer, 06230 Villefranche-sur-Mer, France.
authors: João E
authors: JE
authors: Carvalho
authors: Departamento de Química Orgánica, Universidade de Vigo, 33610 Vigo, Spain.
authors: Susana
authors: S
authors: Alvarez
authors: Departamento de Química Orgánica, Universidade de Vigo, 33610 Vigo, Spain.
authors: Angel R
authors: AR
authors: de Lera
authors: Marine Biology Research Division, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92093-0202 USA.
authors: Linda Z
authors: LZ
authors: Holland
authors: Sorbonne Universités, UPMC Université Paris 06, CNRS, UMR 7009, Laboratoire de Biologie du Développement de Villefranche-sur-Mer, Observatoire Océanologique de Villefranche-sur-Mer, 06230 Villefranche-sur-Mer, France ; CNRS, UMR 7009, Laboratoire de Biologie du Développement de Villefranche-sur-Mer, Observatoire Océanologique de Villefranche-sur-Mer, 06230 Villefranche-sur-Mer, France.
authors: Michael
authors: M
authors: Schubert
keywords: Cephalochordate; Cyp26 function; Tbx1/10; evolution of developmental mechanisms; evolution of the vertebrate head; functional knockdown; pharmacological treatments; pharyngeal patterning; retinoic acid signaling