title: Noggin is required for first pharyngeal arch differentiation in the frog Xenopus tropicalis.
abstract: The dorsal ventral axis of vertebrates requires high BMP activity for ventral development and inhibition of BMP activity for dorsal development. Presumptive dorsal regions of the embryo are protected from the ventralizing activity of BMPs by the secretion of BMP antagonists from the mesoderm. Noggin, one such antagonist, binds BMP ligands and prevents them from binding their receptors, however, a unique role for Noggin in amphibian development has remained unclear. Previously, we used zinc-finger nucleases to mutagenize the noggin locus in Xenopus tropicalis. Here, we report on the phenotype of noggin mutant frogs as a result of breeding null mutations to homozygosity. Early homozygous noggin mutant embryos are indistinguishable from wildtype siblings, with normal neural induction and neural tube closure. However, in late tadpole stages mutants present severe ventral craniofacial defects, notably a fusion of Meckel's cartilage to the palatoquadrate cartilage. Consistent with a noggin loss-of-function, mutants show expansions of BMP target gene expression and the mutant phenotype can be rescued with transient BMP inhibition. These results demonstrate that in amphibians, Noggin is dispensable for early embryonic patterning but is critical for cranial skeletogenesis.
authors.affiliation: Department of Molecular Cell Biology, University of California, Berkeley, Berkeley, CA 94720, United States.
authors.forename: John J
authors.initials: JJ
authors.lastname: Young
authors.affiliation: Department of Molecular Cell Biology, University of California, Berkeley, Berkeley, CA 94720, United States.
authors.forename: Rachel A S
authors.initials: RAS
authors.lastname: Kjolby
authors.affiliation: Department of Molecular Cell Biology, University of California, Berkeley, Berkeley, CA 94720, United States.
authors.forename: Gloria
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Molecular Cell Biology, University of California, Berkeley, Berkeley, CA 94720, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wong
authors.affiliation: Department of Molecular Cell Biology, University of California, Berkeley, Berkeley, CA 94720, United States.
authors.forename: Shu-Wei
authors.initials: SW
authors.lastname: Hsu
authors.affiliation: Department of Molecular Cell Biology, University of California, Berkeley, Berkeley, CA 94720, United States.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Harland
mesh_terms: D000483:Alleles; D000818:Animals; D019521:Body Patterning; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology / Q000502:physiology; D001934:Branchial Region / Q000254:growth & development*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002356:Cartilage / Q000002:abnormalities; D002454:Cell Differentiation; D004625:Embryo, Nonmammalian / Q000378:metabolism / Q000648:ultrastructure; D038681:Follistatin / Q000172:deficiency / Q000235:genetics; D055786:Gene Knockout Techniques; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics; D006720:Homozygote; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics; D007814:Larva; D008334:Mandible / Q000002:abnormalities; D060172:Morpholinos / Q000494:pharmacology; D012886:Skull / Q000002:abnormalities; D014981:Xenopus / Q000196:embryology / Q000254:growth & development*; D029867:Xenopus Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000099176:Noggin Protein
chemical_list: D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D038681:Follistatin; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D060172:Morpholinos; D029867:Xenopus Proteins; D000099176:Noggin Protein; C054234:chordin