Mechanochemical control of mesenchymal condensation and embryonic tooth organ formation. Dev Cell 2011 Oct 18;21(4):758-69
Date
09/20/2011Pubmed ID
21924961Pubmed Central ID
PMC3199351DOI
10.1016/j.devcel.2011.07.006Scopus ID
2-s2.0-80054744142 (requires institutional sign-in at Scopus site) 152 CitationsAbstract
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.
Author List
Mammoto T, Mammoto A, Torisawa YS, Tat T, Gibbs A, Derda R, Mannix R, de Bruijn M, Yung CW, Huh D, Ingber DEAuthors
Akiko Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of WisconsinTadanori Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBiomarkers
Blotting, Western
Cell Adhesion
Cell Movement
Cell Proliferation
Cell Shape
Cells, Cultured
Embryo, Mammalian
Fibroblast Growth Factor 8
Gene Expression Profiling
Mechanotransduction, Cellular
Membrane Proteins
Mesoderm
Mice
Microfluidics
Nerve Tissue Proteins
Odontogenesis
Oligonucleotide Array Sequence Analysis
PAX9 Transcription Factor
Paired Box Transcription Factors
RNA, Messenger
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Tooth
rho GTP-Binding Proteins
rhoA GTP-Binding Protein
