A beta-catenin-independent dorsalization pathway activated by Axin/JNK signaling and antagonized by aida

Dev Cell. 2007 Aug;13(2):268-82. doi: 10.1016/j.devcel.2007.07.006.

Abstract

Axin is a scaffold protein that controls multiple important pathways, including the canonical Wnt pathway and JNK signaling. Here we have identified an Axin-interacting protein, Aida, which blocks Axin-mediated JNK activation by disrupting Axin homodimerization. During investigation of in vivo functions of Axin/JNK signaling and aida in development, it was found that Axin, besides ventralizing activity by facilitating beta-catenin degradation, possesses a dorsalizing activity that is mediated by Axin-induced JNK activation. This dorsalizing activity is repressed when aida is overexpressed in zebrafish embryos. Whereas Aida-MO injection leads to dorsalized embryos, JNK-MO and MKK4-MO can ventralize embryos. The anti-dorsalization activity of aida is conferred by its ability to block Axin-mediated JNK activity. We further demonstrate that dorsoventral patterning regulated by Axin/JNK signaling is independent of maternal or zygotic Wnt signaling. We have thus identified a dorsalization pathway that is exerted by Axin/JNK signaling and its inhibitor Aida during vertebrate embryogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axin Protein
  • Body Patterning* / drug effects
  • COS Cells
  • Carrier Proteins / metabolism*
  • Cell Line
  • Chlorocebus aethiops
  • Dimerization
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / drug effects
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / enzymology
  • Enzyme Activation / drug effects
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • MAP Kinase Signaling System* / drug effects
  • Mice
  • Oligonucleotides, Antisense / pharmacology
  • Phenotype
  • Protein Binding / drug effects
  • Repressor Proteins / chemistry
  • Repressor Proteins / metabolism*
  • Wnt Proteins / metabolism
  • Zebrafish / embryology*
  • Zebrafish / metabolism
  • Zebrafish Proteins / metabolism*
  • beta Catenin / metabolism*

Substances

  • Aida protein, zebrafish
  • Axin Protein
  • Carrier Proteins
  • Oligonucleotides, Antisense
  • Repressor Proteins
  • Wnt Proteins
  • Zebrafish Proteins
  • beta Catenin
  • JNK Mitogen-Activated Protein Kinases