title: Regulation of mesenchymal-to-epithelial transition by PARAXIS during somitogenesis.
abstract: BACKGROUND
  Dynamic alterations in cell shape, migration, and adhesion play a central role in tissue morphogenesis during embryonic development and congenital disease. The mesenchymal-to-epithelial transition that occurs during vertebrate somitogenesis is required for proper patterning of the axial musculoskeletal system. Somitic MET is initiated in the presomitic mesoderm by PARAXIS-dependent changes in cell adhesion, cell polarity, and the composition of the extracellular matrix. However, the target genes downstream of the transcription factor PARAXIS remain poorly described.
  
  
  RESULTS
  A genome-wide comparison of gene expression in the anterior presomitic mesoderm and newly formed somites of Paraxis(-/-) embryos resulted in a set of deregulated genes enriched for factors associated with extracellular matrix and cytoskeletal organization and cell-cell and cell-ECM adhesion. The greatest change in expression was seen in fibroblast activation protein alpha (Fap), encoding a dipeptidyl peptidase capable of increasing fibronectin and collagen fiber organization in extracellular matrix. Further, downstream genes in the Wnt and Notch signaling pathways were downregulated, predicting that PARAXIS participates in positive feedback loops in both pathways.
  
  
  CONCLUSIONS
  These data demonstrate that PARAXIS initiates and stabilizes somite epithelialization by integrating signals from multiple pathways to control the reorganization of the ECM, cytoskeleton, and adhesion junctions during MET.
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, Arizona.
authors.forename: Megan
authors.initials: M
authors.lastname: Rowton
authors.forename: Pilar
authors.initials: P
authors.lastname: Ramos
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Anderson
authors.forename: Jerry M
authors.initials: JM
authors.lastname: Rhee
authors.forename: Heather E
authors.initials: HE
authors.lastname: Cunliffe
authors.forename: Alan
authors.initials: A
authors.lastname: Rawls
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D010450:Endopeptidases; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology*; D019084:Fluorescent Antibody Technique, Indirect; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D019170:Somites / Q000166:cytology* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D010450:Endopeptidases; D018093:Gelatinases; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D014157:Transcription Factors; D000099167:Fibroblast Activation Protein Alpha; C486538:Dmrt2 protein, mouse; C484194:Meox2 protein, mouse; C093234:Tcf15 protein, mouse
keywords: Daam2; Dmrt2; ECM; Fap; MET; Meox2; PARAXIS; TCF15; expression; mesenchymal-to-epithelial transition; somitogenesis