title: Retinoic acid signaling acts via Hox1 to establish the posterior limit of the pharynx in the chordate amphioxus.
abstract: In the invertebrate chordate amphioxus, as in vertebrates, retinoic acid (RA) specifies position along the anterior/posterior axis with elevated RA signaling in the middle third of the endoderm setting the posterior limit of the pharynx. Here we show that AmphiHox1 is also expressed in the middle third of the developing amphioxus endoderm and is activated by RA signaling. Knockdown of AmphiHox1 function with an antisense morpholino oligonucleotide shows that AmphiHox1 mediates the role of RA signaling in setting the posterior limit of the pharynx by repressing expression of pharyngeal markers in the posterior foregut/midgut endoderm. The spatiotemporal expression of these endodermal genes in embryos treated with RA or the RA antagonist BMS009 indicates that Pax1/9, Pitx and Notch are probably more upstream than Otx and Nodal in the hierarchy of genes repressed by RA signaling. This work highlights the potential of amphioxus, a genomically simple, vertebrate-like invertebrate chordate, as a paradigm for understanding gene hierarchies similar to the more complex ones of vertebrates.
authors.affiliation: Ecole Normale Supérieure de Lyon, Laboratoire de Biologie Moléculaire de la Cellule, CNRS-UMR5161/INRA-UMR1237, 46, allée d'Italie, 69364 Lyon Cedex 07, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Schubert
authors.forename: Jr-Kai
authors.initials: JK
authors.lastname: Yu
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Holland
authors.forename: Hector
authors.initials: H
authors.lastname: Escriva
authors.forename: Vincent
authors.initials: V
authors.lastname: Laudet
authors.forename: Linda Z
authors.initials: LZ
authors.lastname: Holland
mesh_terms: D000818:Animals; D002816:Chordata, Nonvertebrate; D004707:Endoderm / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism*; D017403:In Situ Hybridization; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D010614:Pharynx / Q000196:embryology*; D014176:Protein Biosynthesis; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D016376:Oligonucleotides, Antisense; D014157:Transcription Factors; C073547:HOXA4 protein, human; D014212:Tretinoin