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

C  P Heisenberg; C Houart; M Take-Uchi; G  J Rauch; N Young; P Coutinho; I Masai; L Caneparo; M  L Concha; R Geisler; T  C Dale; S  W Wilson; D  L Stemple

doi:10.1101/gad.194301

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

C P Heisenberg, C Houart, M Take-Uchi, G J Rauch, N Young, P Coutinho, I Masai, L Caneparo, M L Concha, R Geisler, T C Dale, S W Wilson, D L Stemple

Developmental Neurobiology

Research output: Contribution to journal › Article › peer-review

226 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1427 - 1434
Number of pages	8
Journal	Genes and Development
Volume	15
Issue number	11
DOIs	https://doi.org/10.1101/gad.194301
Publication status	Published - 2001

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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., & Stemple, D. 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 and Development, 15(11), 1427 - 1434. https://doi.org/10.1101/gad.194301

@article{3e9b9119c3974fc2a5d0015c0ba5f33a,

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.",

author = "Heisenberg, {C P} and C Houart and M Take-Uchi and Rauch, {G J} and N Young and P Coutinho and I Masai and L Caneparo and Concha, {M L} and R Geisler and Dale, {T C} and Wilson, {S W} and Stemple, {D L}",

year = "2001",

doi = "10.1101/gad.194301",

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Heisenberg, CP, Houart, C, Take-Uchi, M, Rauch, GJ, Young, N, Coutinho, P, Masai, I, Caneparo, L, Concha, ML, Geisler, R, Dale, TC, Wilson, SW & Stemple, DL 2001, 'A mutation in the Gsk3-binding domain of zebrafish Masterblind/Axin1 leads to a fate transformation of telencephalon and eyes to diencephalon', Genes and Development, vol. 15, no. 11, pp. 1427 - 1434. https://doi.org/10.1101/gad.194301

TY - JOUR

T1 - A mutation in the Gsk3-binding domain of zebrafish Masterblind/Axin1 leads to a fate transformation of telencephalon and eyes to diencephalon

AU - Heisenberg, C P

AU - Houart, C

AU - Take-Uchi, M

AU - Rauch, G J

AU - Young, N

AU - Coutinho, P

AU - Masai, I

AU - Caneparo, L

AU - Concha, M L

AU - Geisler, R

AU - Dale, T C

AU - Wilson, S W

AU - Stemple, D L

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

U2 - 10.1101/gad.194301

DO - 10.1101/gad.194301

M3 - Article

VL - 15

SP - 1427

EP - 1434

JO - Genes and Development

JF - Genes and Development

IS - 11

ER -

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

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