Abstract
Wnt-4 is expressed in developing neural and renal tissue and is required for renal tubulogenesis in mouse and Xenopus. The function of Wnt-4 in neural differentiation is unknown so far. Here we demonstrate that Wnt-4 is required for eye development in Xenopus laevis. This effect of Wnt-4 depends on the activation of a beta-catenin-independent, noncanonical Wnt signaling pathway. Furthermore, we report the identification of EAF2, a component of the ELL-mediated RNA polymerase II elongation factor complex, as a target gene of Wnt-4 signaling. EAF2 is specifically expressed in the eye and EAF2 expression was dependent on Wnt-4 function. Loss of EAF2 function results in loss of eyes and loss of Wnt-4 function could be rescued by EAF2. In neuralized animal caps, EAF2 has properties characteristic for an RNA polymerase II elongation factor regulating the expression of the eye-specific transcription factor Rx. These data add a new layer of complexity to our understanding of eye development and give further evidence for the importance of noncanonical Wnt pathways in organ development.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Cell Differentiation / genetics
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Cell Differentiation / physiology
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology
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Down-Regulation
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Eye / embryology*
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Eye Proteins / genetics
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Eye Proteins / metabolism
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Gene Expression Regulation, Developmental
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Molecular Sequence Data
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Nervous System / cytology
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Neurons / metabolism
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Oligodeoxyribonucleotides, Antisense / genetics
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Oligodeoxyribonucleotides, Antisense / pharmacology
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Peptide Elongation Factors / genetics
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Peptide Elongation Factors / physiology*
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Proto-Oncogene Proteins / antagonists & inhibitors
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology*
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RNA Polymerase II / genetics
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RNA Polymerase II / physiology
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Signal Transduction*
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription Factors / physiology
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Transcription, Genetic / drug effects
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Wnt Proteins
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Wnt4 Protein
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Xenopus Proteins / genetics
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Xenopus Proteins / physiology*
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Xenopus laevis / embryology*
Substances
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DNA-Binding Proteins
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EAF2 protein, Xenopus
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ELL2 protein, Xenopus
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Eye Proteins
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Homeodomain Proteins
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Oligodeoxyribonucleotides, Antisense
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Peptide Elongation Factors
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Proto-Oncogene Proteins
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Rx protein, vertebrate
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Transcription Factors
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Wnt Proteins
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Wnt4 Protein
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Wnt4 protein, Xenopus
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Wnt4 protein, mouse
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Xenopus Proteins
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RNA Polymerase II
Associated data
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GENBANK/AJ579576
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GENBANK/CA988261