title: Mechanochemical control of mesenchymal condensation and embryonic tooth organ formation.
abstract: Mesenchymal condensation is critical for organogenesis, yet little is known about how this process is controlled. Here we show that Fgf8 and Sema3f, produced by early dental epithelium, respectively, attract and repulse mesenchymal cells, which cause them to pack tightly together during mouse tooth development. Resulting mechanical compaction-induced changes in cell shape induce odontogenic transcription factors (Pax9, Msx1) and a chemical cue (BMP4), and mechanical compression of mesenchyme is sufficient to induce tooth-specific cell fate switching. The inductive effects of cell compaction are mediated by suppression of the mechanical signaling molecule RhoA, and its overexpression prevents odontogenic induction. Thus, the mesenchymal condensation that drives tooth formation is induced by antagonistic epithelial morphogens that manifest their pattern-generating actions mechanically via changes in mesenchymal cell shape and altered mechanotransduction.
authors.affiliation: Vascular Biology Program, Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Tadanori
authors.initials: T
authors.lastname: Mammoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Mammoto
authors.forename: Yu-suke
authors.initials: YS
authors.lastname: Torisawa
authors.forename: Tracy
authors.initials: T
authors.lastname: Tat
authors.forename: Ashley
authors.initials: A
authors.lastname: Gibbs
authors.forename: Ratmir
authors.initials: R
authors.lastname: Derda
authors.forename: Robert
authors.initials: R
authors.lastname: Mannix
authors.forename: Marlieke
authors.initials: M
authors.lastname: de Bruijn
authors.forename: Chong Wing
authors.initials: CW
authors.lastname: Yung
authors.forename: Dongeun
authors.initials: D
authors.lastname: Huh
authors.forename: Donald E
authors.initials: DE
authors.lastname: Ingber
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D048430:Cell Shape; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D040542:Mechanotransduction, Cellular; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000502:physiology*; D051379:Mice; D044085:Microfluidics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009805:Odontogenesis; D020411:Oligonucleotide Array Sequence Analysis; D051764:PAX9 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014070:Tooth / Q000196:embryology* / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein
chemical_list: D015415:Biomarkers; C496457:Fgf8 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D051764:PAX9 Transcription Factor; D051761:Paired Box Transcription Factors; C488759:Pax9 protein, mouse; D012333:RNA, Messenger; C491229:Sema3f protein, mouse; D051524:Fibroblast Growth Factor 8; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein