Mesenchymal condensation-dependent accumulation of collagen VI stabilizes organ-specific cell fates during embryonic tooth formation

Dev Dyn. 2015 Jun;244(6):713-23. doi: 10.1002/dvdy.24264. Epub 2015 Apr 24.


Background: Mechanical compression of cells during mesenchymal condensation triggers cells to undergo odontogenic differentiation during tooth organ formation in the embryo. However, the mechanism by which cell compaction is stabilized over time to ensure correct organ-specific cell fate switching remains unknown.

Results: Here, we show that mesenchymal cell compaction induces accumulation of collagen VI in the extracellular matrix (ECM), which physically stabilizes compressed mesenchymal cell shapes and ensures efficient organ-specific cell fate switching during tooth organ development. Mechanical induction of collagen VI deposition is mediated by signaling through the actin-p38MAPK-SP1 pathway, and the ECM scaffold is stabilized by lysyl oxidase in the condensing mesenchyme. Moreover, perturbation of synthesis or cross-linking of collagen VI alters the size of the condensation in vivo.

Conclusions: These findings suggest that the odontogenic differentiation process that is induced by cell compaction during mesenchymal condensation is stabilized and sustained through mechanically regulated production of collagen VI within the mesenchymal ECM.

Keywords: LOX; SP1; actin; cell compaction; extracellular matrix; mechanical; mesenchymal condensation; organogenesis; p38MAPK; tooth development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Lineage
  • Cell Shape
  • Collagen Type VI / genetics
  • Collagen Type VI / metabolism*
  • Extracellular Matrix Proteins / biosynthesis
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • MAP Kinase Signaling System / drug effects
  • Mesoderm / cytology*
  • Mice
  • Microarray Analysis
  • Molar / embryology*
  • Molar / metabolism
  • Molar / ultrastructure
  • Odontogenesis / physiology*
  • Organ Specificity
  • PAX9 Transcription Factor
  • Paired Box Transcription Factors / biosynthesis
  • Paired Box Transcription Factors / genetics
  • Plicamycin / pharmacology
  • Protein Kinase Inhibitors / pharmacology
  • Protein-Lysine 6-Oxidase / biosynthesis
  • Protein-Lysine 6-Oxidase / genetics
  • Sp1 Transcription Factor / antagonists & inhibitors
  • Sp1 Transcription Factor / physiology
  • Transcription, Genetic
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / physiology


  • Collagen Type VI
  • Extracellular Matrix Proteins
  • PAX9 Transcription Factor
  • Paired Box Transcription Factors
  • Pax9 protein, mouse
  • Protein Kinase Inhibitors
  • Sp1 Transcription Factor
  • Lox protein, mouse
  • Protein-Lysine 6-Oxidase
  • p38 Mitogen-Activated Protein Kinases
  • Plicamycin