title: Maternal xNorrin, a canonical Wnt signaling agonist and TGF-β antagonist, controls early neuroectoderm specification in Xenopus.
abstract: Dorsal-ventral specification in the amphibian embryo is controlled by β-catenin, whose activation in all dorsal cells is dependent on maternal Wnt11. However, it remains unknown whether other maternally secreted factors contribute to β-catenin activation in the dorsal ectoderm. Here, we show that maternal Xenopus Norrin (xNorrin) promotes anterior neural tissue formation in ventralized embryos. Conversely, when xNorrin function is inhibited, early canonical Wnt signaling in the dorsal ectoderm and the early expression of the zygotic neural inducers Chordin, Noggin, and Xnr3 are severely suppressed, causing the loss of anterior structures. In addition, xNorrin potently inhibits BMP- and Nodal/Activin-related functions through direct binding to the ligands. Moreover, a subset of Norrin mutants identified in humans with Norrie disease retain Wnt activation but show defective inhibition of Nodal/Activin-related signaling in mesoderm induction, suggesting that this disinhibition causes Norrie disease. Thus, xNorrin is an unusual molecule that acts on two major signaling pathways, Wnt and TGF-β, in opposite ways and is essential for early neuroectoderm specification.
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Suhong
authors.initials: S
authors.lastname: Xu
authors.forename: Feng
authors.initials: F
authors.lastname: Cheng
authors.forename: Juan
authors.initials: J
authors.lastname: Liang
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001766:Blindness / Q000151:congenital / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D017124:Conserved Sequence; D004625:Embryo, Nonmammalian / Q000378:metabolism / Q000473:pathology; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D040181:Genetic Diseases, X-Linked; D006801:Humans; D008024:Ligands; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D009422:Nervous System Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D054258:Neural Plate / Q000196:embryology* / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding; D012162:Retinal Degeneration; D013036:Spasms, Infantile / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D014981:Xenopus / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D000099176:Noggin Protein
chemical_list: D055415:Bone Morphogenetic Protein 4; D002352:Carrier Proteins; D008024:Ligands; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D029867:Xenopus Proteins; D000099176:Noggin Protein; C525812:bmp4 protein, Xenopus; C094620:nodal3.1 protein, Xenopus; C512785:wnt11b protein, Xenopus