Cp. Heisenberg et al., A mutation in the Gsk3-binding domain of zebrafish Masterblind/Axin1 leadsto a fate transformation of telencephalon and eyes to diencephalon, GENE DEV, 15(11), 2001, pp. 1427-1434
Zebrafish embryos homozygous for the masterblind (mb1) mutation exhibit a s
triking 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
mb1(-/-) 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-depen
dent transcription. Therefore, Gsk3 activity may be decreased in mbl(-/-) e
mbryos and in support of this possibility, overexpression of either wild-ty
pe Axin1 or Gsk3 beta can restore eye and telencephalic fates to mb1(-/-) e
mbryos. Our data reveal a crucial role for Axin1-dependent inhibition of th
e Wnt pathway in the early regional subdivision of the anterior neural plat
e into telencephalic, diencephalic, and eye-forming territories.