PMID- 11861759 OWN - NLM STAT- MEDLINE DCOM- 20021230 LR - 20220215 IS - 0021-9533 (Print) IS - 0021-9533 (Linking) VI - 115 IP - Pt 3 DP - 2002 Feb 1 TI - Pax3 induces cell aggregation and regulates phenotypic mesenchymal-epithelial interconversion. PG - 517-29 AB - Paired box-containing transcription factors play fundamental roles in pattern formation during embryonic development of diverse organisms ranging from Drosophila to mammals. Although mutations to Pax3 and other Pax-family genes in both mice and humans result in numerous tissue-specific morphological defects, little is known about the cellular processes that Pax genes regulate. We show that extopic Pax3 expression in two distinct phenotypically mesenchymal mammalian cell lines induces the formation of multi-layered condensed cell aggregates with epithelial characteristics. For one of these lines, we showed further that Pax3-induced cell aggregation is accompanied by specific morphological changes, including a significant reduction in cell size, altered cell shape and dramatic alterations to both membrane and cytoskeleton architecture. In addition to mediating a phenotypic mesenchymal-to-epithelial transition, Pax3 also establishes the conditions in these cells for a subsequent hepatocyte growth factor/scatter factor (HGF/SF)-induced phenotypic epithelial-to-mesenchymal transition. Thus, our data show a novel morphogenetic activity for Pax3 which, when absent in vivo, is predicted to give rise to the observed structural defects in somites and the neural tube during embryonic development. FAU - Wiggan, O'Neil AU - Wiggan O AD - Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, M5S 1A8 Canada. FAU - Fadel, Marc P AU - Fadel MP FAU - Hamel, Paul A AU - Hamel PA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Cell Sci JT - Journal of cell science JID - 0052457 RN - 0 (Actins) RN - 0 (Cadherins) RN - 0 (Culture Media, Conditioned) RN - 0 (Cytoskeletal Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (Membrane Proteins) RN - 0 (PAX3 Transcription Factor) RN - 0 (PAX3 protein, human) RN - 0 (Paired Box Transcription Factors) RN - 0 (Phosphoproteins) RN - 0 (TJP1 protein, human) RN - 0 (Tjp1 protein, mouse) RN - 0 (Transcription Factors) RN - 0 (Zonula Occludens-1 Protein) RN - 138016-91-8 (Pax3 protein, mouse) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) SB - IM MH - Actins/metabolism MH - Adenoviridae/genetics/metabolism MH - Animals MH - COS Cells MH - Cadherins/metabolism MH - Cell Aggregation/*physiology MH - Cell Polarity MH - Cell Size MH - Culture Media, Conditioned MH - Cytoskeletal Proteins/metabolism MH - Cytoskeleton/metabolism MH - DNA-Binding Proteins/*metabolism MH - Epithelium/*metabolism MH - Genes, Reporter MH - Hepatocyte Growth Factor/metabolism MH - Humans MH - Immunohistochemistry MH - Membrane Proteins/metabolism MH - Mesoderm/*metabolism MH - Microtubules/metabolism MH - Osteosarcoma MH - PAX3 Transcription Factor MH - Paired Box Transcription Factors MH - Phenotype MH - Phosphoproteins/metabolism MH - Proto-Oncogene Proteins c-met/metabolism MH - Rhabdomyosarcoma MH - Transcription Factors/*metabolism MH - Tumor Cells, Cultured MH - Zonula Occludens-1 Protein EDAT- 2002/02/28 10:00 MHDA- 2002/12/31 04:00 CRDT- 2002/02/28 10:00 PHST- 2002/02/28 10:00 [pubmed] PHST- 2002/12/31 04:00 [medline] PHST- 2002/02/28 10:00 [entrez] AID - 10.1242/jcs.115.3.517 [doi] PST - ppublish SO - J Cell Sci. 2002 Feb 1;115(Pt 3):517-29. doi: 10.1242/jcs.115.3.517.