Pax3 regulates morphogenetic cell behavior in vitro coincident with activation of a PCP/non-canonical Wnt-signaling cascade

• Published in: Journal of cell science Vol. 115; no. Pt 3; pp. 531 - 541
• Main Authors: Wiggan, O'Neil, Hamel, Paul A
• Format: Journal Article
• Language: English
• Published: England 01.02.2002
• Subjects: Actins - metabolism; Adaptor Proteins, Signal Transducing; Adenoviridae - genetics; Adenoviridae - metabolism; Animals; Cell Aggregation - physiology; Cell Movement - physiology; Cell Polarity; Cell Size; Dishevelled Proteins; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Enzyme Activation; Focal Adhesions - metabolism; Frizzled Receptors; Genes, Reporter; Humans; Immunohistochemistry; JNK Mitogen-Activated Protein Kinases; Mice; Mitogen-Activated Protein Kinases - metabolism; Osteosarcoma; Paired Box Transcription Factors; PAX3 Transcription Factor; Phosphoproteins - metabolism; Proteins - metabolism; Proto-Oncogene Proteins - metabolism; Signal Transduction - physiology; Transcription Factors; Tumor Cells, Cultured; Vinculin - metabolism; Wnt Proteins; Zebrafish Proteins
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.115.3.531

Mutations to Pax3 and other Pax family genes in both mice and humans result in numerous tissue-specific morphological defects. Little is known, however, about the cellular and molecular mechanisms by which Pax genes regulate morphogenesis. We previously showed that Pax3 induces cell aggregation and a mesenchymal-to-epithelial transition in Saos-2 cells. We show here that Pax3-induced aggregates arise through the formation of distinct structures involving cell rearrangements and cell behaviors resembling those that occur during gastrulation and neurulation known as convergent extension. During these Pax3-induced processes, Dishevelled and Frizzled are localized to the actin cytoskeleton and both proteins coimmunoprecipitate focal adhesion components from detergent-insoluble cell fractions. We show further that these Pax3-induced cell movements are associated with activation of a Wnt-signaling cascade, resulting in induction and activation of c-Jun-N-terminal kinase/stress activated protein kinase (JNK/SAPK). All of these Wnt-signaling factors exhibit altered subcellular distribution in Pax3-expressing cells. In particular, we show the localization of JNK/SAPK to both the nucleus and to cytoplasmic multi-vesicular structures. These data show that Pax3 regulates morphogenetic cell behavior and that regulation of a conserved, planar cell polarity/noncanonical Wnt-signaling cascade entailing JNK activation is a function of Pax3 activity.