Noncanonical Wnt-4 signaling and EAF2 are required for eye development in Xenopus laevis.
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.
Maurus
Daniel
D
Department of Biochemistry, University of Ulm, Ulm, Germany.
Héligon
Christophe
C
Bürger-Schwärzler
Anja
A
Brändli
André W
AW
Kühl
Michael
M
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D015536:Down-Regulation; D005123:Eye / Q000196:embryology*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009420:Nervous System / Q000166:cytology; D009474:Neurons / Q000378:metabolism; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D010445:Peptide Elongation Factors / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D012319:RNA Polymerase II / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects; D051153:Wnt Proteins; D060528:Wnt4 Protein; D029867:Xenopus Proteins / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology*
D004268:DNA-Binding Proteins; C500886:EAF2 protein, Xenopus; C488332:ELL2 protein, Xenopus; D005136:Eye Proteins; D018398:Homeodomain Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D010445:Peptide Elongation Factors; D011518:Proto-Oncogene Proteins; C111251:Rx protein, vertebrate; D014157:Transcription Factors; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555584:Wnt4 protein, Xenopus; C555582:Wnt4 protein, mouse; D029867:Xenopus Proteins; D012319:RNA Polymerase II