title: A mutation in the Gsk3-binding domain of zebrafish Masterblind/Axin1 leads to a fate transformation of telencephalon and eyes to diencephalon.
abstract: Zebrafish embryos homozygous for the masterblind (mbl) mutation exhibit a striking phenotype in which the eyes and telencephalon are reduced or absent and diencephalic fates expand to the front of the brain. Here we show that mbl(-/-) embryos carry an amino-acid change at a conserved site in the Wnt pathway scaffolding protein, Axin1. The amino-acid substitution present in the mbl allele abolishes the binding of Axin to Gsk3 and affects Tcf-dependent transcription. Therefore, Gsk3 activity may be decreased in mbl(-/-) embryos and in support of this possibility, overexpression of either wild-type Axin1 or Gsk3beta can restore eye and telencephalic fates to mbl(-/-) embryos. Our data reveal a crucial role for Axin1-dependent inhibition of the Wnt pathway in the early regional subdivision of the anterior neural plate into telencephalic, diencephalic, and eye-forming territories.
authors.affiliation: Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, UK.
authors.forename: C P
authors.initials: CP
authors.lastname: Heisenberg
authors.forename: C
authors.initials: C
authors.lastname: Houart
authors.forename: M
authors.initials: M
authors.lastname: Take-Uchi
authors.forename: G J
authors.initials: GJ
authors.lastname: Rauch
authors.forename: N
authors.initials: N
authors.lastname: Young
authors.forename: P
authors.initials: P
authors.lastname: Coutinho
authors.forename: I
authors.initials: I
authors.lastname: Masai
authors.forename: L
authors.initials: L
authors.lastname: Caneparo
authors.forename: M L
authors.initials: ML
authors.lastname: Concha
authors.forename: R
authors.initials: R
authors.lastname: Geisler
authors.forename: T C
authors.initials: TC
authors.lastname: Dale
authors.forename: S W
authors.initials: SW
authors.lastname: Wilson
authors.forename: D L
authors.initials: DL
authors.lastname: Stemple
mesh_terms: D000818:Animals; D060466:Axin Protein; D019521:Body Patterning / Q000235:genetics* / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics* / Q000378:metabolism; D017124:Conserved Sequence; D004027:Diencephalon / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D004625:Embryo, Nonmammalian; D005123:Eye / Q000196:embryology* / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3; D017403:In Situ Hybridization; D009154:Mutation; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins; D015398:Signal Transduction; D013687:Telencephalon / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D051153:Wnt Proteins; D015027:Zebrafish; D029961:Zebrafish Proteins
chemical_list: D060466:Axin Protein; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C094522:wnt8b protein, zebrafish; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3