ZFIN ID: ZDB-PUB-010705-2
A mutation in the Gsk3-binding domain of zebrafish Masterblind/Axin1 leads to a fate transformation of telencephalon and eyes to diencephalon
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.
Date: 2001
Source: Genes and 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* (all 31) expand
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.
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