title: Sprouty2 controls proliferation of palate mesenchymal cells via fibroblast growth factor signaling.
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.
authors.affiliation: Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Matsumura
authors.forename: Takaharu
authors.initials: T
authors.lastname: Taketomi
authors.forename: Keigo
authors.initials: K
authors.lastname: Yoshizaki
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Arai
authors.forename: Terukazu
authors.initials: T
authors.lastname: Sanui
authors.forename: Daigo
authors.initials: D
authors.lastname: Yoshiga
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Seiji
authors.initials: S
authors.lastname: Nakamura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins; D051957:MSX1 Transcription Factor / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D051761:Paired Box Transcription Factors / Q000235:genetics; D010159:Palate / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C513242:Etv5 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D051957:MSX1 Transcription Factor; D008565:Membrane Proteins; C484084:Msx1 protein, mouse; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C101485:homeobox protein PITX1; D005346:Fibroblast Growth Factors; D017346:Protein Serine-Threonine Kinases; C118389:Spry2 protein, mouse