PUBLICATION

A mutation in the Gsk3-binding domain of zebrafish Masterblind/Axin1 leads to a fate transformation of telencephalon and eyes to diencephalon

Authors
Heisenberg, C.P., Houart, C., Take-uchi, M., Rauch, G.J., Young, N., Coutinho, P., Masai, I., Caneparo, L., Concha, M.L., Geisler, R., Dale, T.C., Wilson, S.W., and Stemple, D.L.
ID
ZDB-PUB-010705-2
Date
2001
Source
Genes & Development   15(11): 1427-1434 (Journal)
Registered Authors
Caneparo, Luca, Concha, Miguel, Coutinho, Pedro, Geisler, Robert, Heisenberg, Carl-Philipp, Houart, Corinne, Masai, Ichiro, Rauch, Gerd-Jörg, Stemple, Derek L., Take-uchi, Masaya, Wilson, Steve
Keywords
Axin; Wnt; forebrain; zebrafish
MeSH Terms
  • Animals
  • Axin Protein
  • Body Patterning/genetics*
  • Body Patterning/physiology
  • Calcium-Calmodulin-Dependent Protein Kinases/genetics*
  • Calcium-Calmodulin-Dependent Protein Kinases/metabolism
  • Conserved Sequence
  • Diencephalon/embryology*
  • Diencephalon/growth & development
  • Diencephalon/metabolism
  • Embryo, Nonmammalian
  • Eye/embryology*
  • Eye/metabolism
  • Glycogen Synthase Kinase 3
  • In Situ Hybridization
  • Mutation
  • Precipitin Tests
  • Protein Binding
  • Protein Structure, Tertiary
  • Proteins/genetics*
  • Proteins/metabolism
  • Proto-Oncogene Proteins/genetics
  • Proto-Oncogene Proteins/physiology
  • Repressor Proteins*
  • Signal Transduction
  • Telencephalon/embryology*
  • Telencephalon/growth & development
  • Telencephalon/metabolism
  • Wnt Proteins
  • Zebrafish
  • Zebrafish Proteins*
PubMed
11390362 Full text @ Genes & Dev.
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.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
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Mapping