Abstract
Here we show that XsalF, a frog homolog of the Drosophila homeotic selector spalt, plays an essential role for the forebrain/midbrain determination in Xenopus. XsalF overexpression expands the domain of forebrain/midbrain genes and suppresses midbrain/hindbrain boundary (MHB) markers and anterior hindbrain genes. Loss-of-function studies show that XsalF is essential for the expression of the forebrain/midbrain genes and for the repression of the caudal genes. Interestingly, XsalF functions by antagonizing canonical Wnt signaling, which promotes caudalization of neural tissues. XsalF is required for anterior-specific expressions of GSK3beta and Tcf3, genes encoding antagonistic effectors of Wnt signaling. Loss-of-function phenotypes of GSK3beta and Tcf3 mimic those of XsalF while injections of GSK3beta and Tcf3 rescue loss-of-function phenotypes of XsalF. These findings suggest that the forebrain/midbrain-specific gene XsalF negatively controls cellular responsiveness to posteriorizing Wnt signals by regulating region-specific GSK3beta and Tcf3 expression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brain / cytology
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Brain / embryology*
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Brain / metabolism*
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Cell Lineage / genetics
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DNA, Complementary / analysis
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DNA, Complementary / genetics
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Drosophila Proteins
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Ectoderm / cytology
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Ectoderm / metabolism*
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Embryo, Nonmammalian
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Gene Expression Regulation, Developmental / genetics
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Glycogen Synthase Kinase 3 / genetics
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Glycogen Synthase Kinase 3 / metabolism
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Glycogen Synthase Kinase 3 / pharmacology
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Glycogen Synthase Kinase 3 beta
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HMGB Proteins / genetics
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HMGB Proteins / metabolism
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HMGB Proteins / pharmacology
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Mesencephalon / cytology
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Mesencephalon / embryology
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Mesencephalon / metabolism
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Molecular Sequence Data
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Mutation / genetics
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Phenotype
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Prosencephalon / cytology
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Prosencephalon / embryology
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Prosencephalon / metabolism
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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RNA, Messenger / metabolism
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RNA, Messenger / pharmacology
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Sequence Homology, Amino Acid
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Sequence Homology, Nucleic Acid
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Signal Transduction / genetics
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TCF Transcription Factors
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Transcription Factor 7-Like 1 Protein
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Transcription Factors / genetics
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Transcription Factors / isolation & purification
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Transcription Factors / metabolism*
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Transcription Factors / pharmacology
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Wnt Proteins
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Xenopus Proteins / genetics
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Xenopus Proteins / isolation & purification
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Xenopus Proteins / metabolism*
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Xenopus laevis / embryology*
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Xenopus laevis / metabolism*
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Zinc Fingers / genetics
Substances
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DNA, Complementary
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Drosophila Proteins
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HMGB Proteins
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Homeodomain Proteins
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Proto-Oncogene Proteins
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RNA, Messenger
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SALL2 protein, Xenopus
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TCF Transcription Factors
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Transcription Factor 7-Like 1 Protein
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Transcription Factors
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Wnt Proteins
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Xenopus Proteins
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salm protein, Drosophila
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Glycogen Synthase Kinase 3 beta
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Glycogen Synthase Kinase 3
Associated data
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GENBANK/AY508953
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GENBANK/AY508954