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EMBO J ; 24(6): 1181-91, 2005 Mar 23.
Article in English | MEDLINE | ID: mdl-15775981

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.


Subject(s)
Eye/embryology , Peptide Elongation Factors/physiology , Proto-Oncogene Proteins/physiology , Signal Transduction , Xenopus Proteins/physiology , Xenopus laevis/embryology , Amino Acid Sequence , Animals , Cell Differentiation/genetics , Cell Differentiation/physiology , DNA-Binding Proteins/genetics , DNA-Binding Proteins/physiology , Down-Regulation , Eye Proteins/genetics , Eye Proteins/metabolism , Gene Expression Regulation, Developmental , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Molecular Sequence Data , Nervous System/cytology , Neurons/metabolism , Oligodeoxyribonucleotides, Antisense/genetics , Oligodeoxyribonucleotides, Antisense/pharmacology , Peptide Elongation Factors/genetics , Proto-Oncogene Proteins/antagonists & inhibitors , Proto-Oncogene Proteins/genetics , RNA Polymerase II/genetics , RNA Polymerase II/physiology , Transcription Factors/genetics , Transcription Factors/metabolism , Transcription Factors/physiology , Transcription, Genetic/drug effects , Wnt Proteins , Wnt4 Protein , Xenopus Proteins/genetics
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