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Andoniadou CL
,
Signore M
,
Young RM
,
Gaston-Massuet C
,
Wilson SW
,
Fuchs E
,
Martinez-Barbera JP
.
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The Wnt/β-catenin pathway plays an essential role during regionalisation of the vertebrate neural plate and its inhibition in the most anterior neural ectoderm is required for normal forebrain development. Hesx1 is a conserved vertebrate-specific transcription factor that is required for forebrain development in Xenopus, mice and humans. Mouse embryos deficient for Hesx1 exhibit a variable degree of forebrain defects, but the molecular mechanisms underlying these defects are not fully understood. Here, we show that injection of a hesx1 morpholino into a 'sensitised' zygotic headless (tcf3) mutant background leads to severe forebrain and eye defects, suggesting an interaction between Hesx1 and the Wnt pathway during zebrafish forebrain development. Consistent with a requirement for Wnt signalling repression, we highlight a synergistic gene dosage-dependent interaction between Hesx1 and Tcf3, a transcriptional repressor of Wnt target genes, to maintain anterior forebrain identity during mouse embryogenesis. In addition, we reveal that Tcf3 is essential within the neural ectoderm to maintain anterior character and that its interaction with Hesx1 ensures the repression of Wnt targets in the developing forebrain. By employing a conditional loss-of-function approach in mouse, we demonstrate that deletion of β-catenin, and concomitant reduction of Wnt signalling in the developing anterior forebrain of Hesx1-deficient embryos, leads to a significant rescue of the forebrain defects. Finally, transcriptional profiling of anterior forebrain precursors from mouse embryos expressing eGFP from the Hesx1 locus provides molecular evidence supporting a novel function of Hesx1 in mediating repression of Wnt/β-catenin target activation in the developing forebrain.
Andoniadou,
Lack of the murine homeobox gene Hesx1 leads to a posterior transformation of the anterior forebrain.
2007, Pubmed
Andoniadou,
Lack of the murine homeobox gene Hesx1 leads to a posterior transformation of the anterior forebrain.
2007,
Pubmed
Brannon,
XCtBP is a XTcf-3 co-repressor with roles throughout Xenopus development.
1999,
Pubmed
,
Xenbase
Brantjes,
All Tcf HMG box transcription factors interact with Groucho-related co-repressors.
2001,
Pubmed
Brault,
Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development.
2001,
Pubmed
Braun,
Wnt signaling is required at distinct stages of development for the induction of the posterior forebrain.
2003,
Pubmed
Buchert,
Genetic dissection of differential signaling threshold requirements for the Wnt/beta-catenin pathway in vivo.
2010,
Pubmed
Carvalho,
Corepressors TLE1 and TLE3 interact with HESX1 and PROP1.
2010,
Pubmed
Dasen,
Temporal regulation of a paired-like homeodomain repressor/TLE corepressor complex and a related activator is required for pituitary organogenesis.
2001,
Pubmed
Dattani,
Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse.
1998,
Pubmed
Dorsky,
Two tcf3 genes cooperate to pattern the zebrafish brain.
2003,
Pubmed
Eagleson,
Disruption of Foxg1 expression by knock-in of cre recombinase: effects on the development of the mouse telencephalon.
2007,
Pubmed
Ermakova,
The homeobox gene, Xanf-1, can control both neural differentiation and patterning in the presumptive anterior neurectoderm of the Xenopus laevis embryo.
1999,
Pubmed
,
Xenbase
Ermakova,
The homeodomain factor Xanf represses expression of genes in the presumptive rostral forebrain that specify more caudal brain regions.
2007,
Pubmed
,
Xenbase
Felix,
The TALE class homeobox gene Smed-prep defines the anterior compartment for head regeneration.
2010,
Pubmed
Fredieu,
Xwnt-8 and lithium can act upon either dorsal mesodermal or neurectodermal cells to cause a loss of forebrain in Xenopus embryos.
1997,
Pubmed
,
Xenbase
Galceran,
Wnt3a-/--like phenotype and limb deficiency in Lef1(-/-)Tcf1(-/-) mice.
1999,
Pubmed
Garaventa,
131I-metaiodobenzylguanidine (131I-MIBG) therapy for residual neuroblastoma: a mono-institutional experience with 43 patients.
1999,
Pubmed
Gaston-Massuet,
Genetic interaction between the homeobox transcription factors HESX1 and SIX3 is required for normal pituitary development.
2008,
Pubmed
Glinka,
Head induction by simultaneous repression of Bmp and Wnt signalling in Xenopus.
1997,
Pubmed
,
Xenbase
Haegel,
Lack of beta-catenin affects mouse development at gastrulation.
1995,
Pubmed
Heisenberg,
A mutation in the Gsk3-binding domain of zebrafish Masterblind/Axin1 leads to a fate transformation of telencephalon and eyes to diencephalon.
2001,
Pubmed
Houart,
Establishment of the telencephalon during gastrulation by local antagonism of Wnt signaling.
2002,
Pubmed
Houston,
Repression of organizer genes in dorsal and ventral Xenopus cells mediated by maternal XTcf3.
2002,
Pubmed
,
Xenbase
Ivanova,
In vivo genetic ablation by Cre-mediated expression of diphtheria toxin fragment A.
2005,
Pubmed
Junghans,
Beta-catenin-mediated cell-adhesion is vital for embryonic forebrain development.
2005,
Pubmed
Kazanskaya,
The role of Xenopus dickkopf1 in prechordal plate specification and neural patterning.
2000,
Pubmed
,
Xenbase
Kazanskaya,
Anf: a novel class of vertebrate homeobox genes expressed at the anterior end of the main embryonic axis.
1997,
Pubmed
,
Xenbase
Kelberman,
Genetic regulation of pituitary gland development in human and mouse.
2009,
Pubmed
Kim,
Repressor activity of Headless/Tcf3 is essential for vertebrate head formation.
2000,
Pubmed
Kimmel,
Stages of embryonic development of the zebrafish.
1995,
Pubmed
,
Xenbase
Kimura,
Visceral endoderm mediates forebrain development by suppressing posteriorizing signals.
2000,
Pubmed
Kudoh,
Distinct roles for Fgf, Wnt and retinoic acid in posteriorizing the neural ectoderm.
2002,
Pubmed
Lagutin,
Six3 repression of Wnt signaling in the anterior neuroectoderm is essential for vertebrate forebrain development.
2003,
Pubmed
Maretto,
Mapping Wnt/beta-catenin signaling during mouse development and in colorectal tumors.
2003,
Pubmed
Martinez-Barbera,
The homeobox gene Hesx1 is required in the anterior neural ectoderm for normal forebrain formation.
2000,
Pubmed
Merrill,
Tcf3: a transcriptional regulator of axis induction in the early embryo.
2004,
Pubmed
Meyers,
An Fgf8 mutant allelic series generated by Cre- and Flp-mediated recombination.
1998,
Pubmed
Nguyen,
Tcf3 and Tcf4 are essential for long-term homeostasis of skin epithelia.
2009,
Pubmed
Paek,
β-Catenin-dependent FGF signaling sustains cell survival in the anterior embryonic head by countering Smad4.
2011,
Pubmed
Perea-Gomez,
Role of the anterior visceral endoderm in restricting posterior signals in the mouse embryo.
2001,
Pubmed
Piccolo,
The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP and Wnt signals.
1999,
Pubmed
,
Xenbase
Rodríguez,
High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP.
2000,
Pubmed
Sajedi,
Analysis of mouse models carrying the I26T and R160C substitutions in the transcriptional repressor HESX1 as models for septo-optic dysplasia and hypopituitarism.
2008,
Pubmed
Satoh,
Anteriorization of neural fate by inhibitor of beta-catenin and T cell factor (ICAT), a negative regulator of Wnt signaling.
2004,
Pubmed
Shimamura,
Inductive interactions direct early regionalization of the mouse forebrain.
1997,
Pubmed
Spieler,
Involvement of Pax6 and Otx2 in the forebrain-specific regulation of the vertebrate homeobox gene ANF/Hesx1.
2004,
Pubmed
Srinivas,
Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus.
2001,
Pubmed
Thomas,
Anterior primitive endoderm may be responsible for patterning the anterior neural plate in the mouse embryo.
1996,
Pubmed
van Amerongen,
Towards an integrated view of Wnt signaling in development.
2009,
Pubmed
van de Water,
Ectopic Wnt signal determines the eyeless phenotype of zebrafish masterblind mutant.
2001,
Pubmed
Wang,
The canonical Wnt/β-catenin signaling pathway regulates Fgf signaling for early facial development.
2011,
Pubmed
Weidinger,
The Sp1-related transcription factors sp5 and sp5-like act downstream of Wnt/beta-catenin signaling in mesoderm and neuroectoderm patterning.
2005,
Pubmed
Wilson,
Early steps in the development of the forebrain.
2004,
Pubmed
Yamamoto,
Shisa promotes head formation through the inhibition of receptor protein maturation for the caudalizing factors, Wnt and FGF.
2005,
Pubmed
,
Xenbase
