A mutation in the Gsk3-binding domain of zebrafish Masterblind/Axin1 leads to a fate transformation of telencephalon and eyes to diencephalon.
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.
Heisenberg
C P
CP
Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, UK.
Houart
C
C
Take-Uchi
M
M
Rauch
G J
GJ
Young
N
N
Coutinho
P
P
Masai
I
I
Caneparo
L
L
Concha
M L
ML
Geisler
R
R
Dale
T C
TC
Wilson
S W
SW
Stemple
D L
DL
D000818:Animals; D060466:Axin Protein; D019521:Body Patterning / Q000235:genetics* / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics* / Q000378:metabolism; D017124:Conserved Sequence; D004027:Diencephalon / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D004625:Embryo, Nonmammalian; D005123:Eye / Q000196:embryology* / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3; D017403:In Situ Hybridization; D009154:Mutation; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins; D015398:Signal Transduction; D013687:Telencephalon / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D051153:Wnt Proteins; D015027:Zebrafish; D029961:Zebrafish Proteins
D060466:Axin Protein; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C094522:wnt8b protein, zebrafish; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3