BMP4 and FGF strongly induce differentiation of mouse ES cells into oral ectoderm

Stem Cell Res. 2015 Sep;15(2):290-8. doi: 10.1016/j.scr.2015.06.011. Epub 2015 Jul 2.


During embryonic development, oral ectoderm differentiates into the adenohypophysis, dental epithelia, salivary glands, and nasal pit. Few reports exist concerning the induction of oral ectoderm from embryonic stem (ES) cells. Generally, any lot differences in fetal bovine serum (FBS) and serum replacer may affect the induction of ES cell-differentiation. Using a previously established culture strategy for differentiation, the proportion of cell aggregates containing Pitx1+ oral ectoderm varied widely between 9-36% when several different lots of FBS or serum replacer were used. We therefore tried to enhance the differentiation method. We found that bone morphogenetic protein (BMP) 4 and fibroblast growth factor (FGF) treatments improved oral ectoderm induction. Such treatment also improved the differentiation of oral ectoderm into the adenohypophysis. Furthermore, increased BMP4 treatment induced dental epithelium and mesenchyme. Such differentiation suggests that the Pitx1+ layer displays similar properties to oral ectoderm, as found in vivo. Differentiation of ES cells into oral ectoderm using different lots of FBS and serum replacer increased 78-90% after treatment with BMP4 and FGF. In summary, we have established a robust strategy for the induction of oral ectoderm differentiation from mouse ES cells.

Keywords: Adenohypophysis; BMP4; Dental primordium; Embryonic stem cells; FGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 4 / pharmacology*
  • Cell Differentiation / drug effects*
  • Ectoderm / cytology
  • Eye Proteins / genetics
  • Eye Proteins / metabolism
  • Fibroblast Growth Factors / pharmacology*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • LIM-Homeodomain Proteins / genetics
  • LIM-Homeodomain Proteins / metabolism
  • Mice
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / metabolism
  • Paired Box Transcription Factors / genetics
  • Paired Box Transcription Factors / metabolism
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • Transcription Factor Pit-1 / genetics
  • Transcription Factor Pit-1 / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Bone Morphogenetic Protein 4
  • Eye Proteins
  • Homeodomain Proteins
  • LIM-Homeodomain Proteins
  • Lhx3 protein
  • Paired Box Transcription Factors
  • Pit1 protein, mouse
  • Rax protein, mouse
  • T-Box Domain Proteins
  • Tbx19 protein, mouse
  • Transcription Factor Pit-1
  • Transcription Factors
  • homeobox protein PITX1
  • homeobox protein PITX2
  • Fibroblast Growth Factors