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, Corinne, Take-uchi, Masaya, Rauch, Gerd-Jörg, Young, Neville, Coutinho, Pedro, Masai, Ichiro, Caneparo, Luca, Concha, Miguel L., Geisler, Robert, Dale, Trevor Clive ORCID: https://orcid.org/0000-0002-4880-9963, Wilson, Stephen W. and Stemple, Derek L. 2001. A mutation in the Gsk3-binding domain of zebrafish Masterblind/Axin1 leads to a fate transformation of telencephalon and eyes to diencephalon. Genes & Development 15 (11) , pp. 1427-1434. 10.1101/gad.194301

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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 Gsk3β 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
ISSN:	0890-9369
Funders:	Cancer Research UK
Last Modified:	22 Jun 2023 10:01
URI:	https://orca.cardiff.ac.uk/id/eprint/61738

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