Sprouty2 controls proliferation of palate mesenchymal cells via fibroblast growth factor signaling

Biochem Biophys Res Commun. 2011 Jan 28;404(4):1076-82. doi: 10.1016/j.bbrc.2010.12.116. Epub 2010 Dec 30.

Abstract

Cleft palate is one of the most common craniofacial deformities. The fibroblast growth factor (FGF) plays a central role in reciprocal interactions between adjacent tissues during palatal development, and the FGF signaling pathway has been shown to be inhibited by members of the Sprouty protein family. In this study, we report the incidence of cleft palate, possibly caused by failure of palatal shelf elevation, in Sprouty2-deficient (KO) mice. Sprouty2-deficient palates fused completely in palatal organ culture. However, palate mesenchymal cell proliferation estimated by Ki-67 staining was increased in Sprouty2 KO mice compared with WT mice. Sprouty2-null palates expressed higher levels of FGF target genes, such as Msx1, Etv5, and Ptx1 than WT controls. Furthermore, proliferation and the extracellular signal-regulated kinase (Erk) activation in response to FGF was enhanced in palate mesenchymal cells transfected with Sprouty2 small interfering RNA. These results suggest that Sprouty2 regulates palate mesenchymal cell proliferation via FGF signaling and is involved in palatal shelf elevation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Apoptosis / genetics
  • Cell Proliferation
  • DNA-Binding Proteins / genetics
  • Female
  • Fibroblast Growth Factors / metabolism*
  • Gene Expression Regulation, Developmental
  • Intracellular Signaling Peptides and Proteins
  • MSX1 Transcription Factor / genetics
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mesoderm / cytology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organ Culture Techniques
  • Paired Box Transcription Factors / genetics
  • Palate / cytology
  • Palate / embryology*
  • Palate / metabolism
  • Protein-Serine-Threonine Kinases
  • Signal Transduction
  • Transcription Factors / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • Etv5 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • MSX1 Transcription Factor
  • Membrane Proteins
  • Msx1 protein, mouse
  • Paired Box Transcription Factors
  • Transcription Factors
  • homeobox protein PITX1
  • Fibroblast Growth Factors
  • Protein-Serine-Threonine Kinases
  • Spry2 protein, mouse