title: Efficient regulation of branching morphogenesis via fibroblast growth factor receptor 2c in early-stage embryonic mouse salivary glands.
abstract: Salivary gland (SG) defects have a wide range of health implications, including xerostomia, bacterial infections, and oral health issues. Branching morphogenesis is critical for SG development. A clear understanding of the mechanisms underlying this process will accelerate SG regeneration studies. Fibroblast growth factor receptor 2 (FGFR2) interacts with multiple fibroblast growth factors (FGFs), which promote development. FGFR2 consists of two isoforms, FGFR2b and FGFR2c. FGFR2b is critical for SG development, but little is known about the expression and function of FGFR2c. We investigated the expression of all FGFR family members in fetal SGs between embryonic day 12.5 (E12.5) and E18.5. Based on RT-PCR, we observed an increase in the expression of not only Fgfr2b, but also Fgfr2c in early-stage embryonic mouse SGs, suggesting that FGFR2c is related to SG development. The branch number decreased in response to exogenous FGF2 stimulation, and this effect was suppressed by a mouse anti-FGFR2c neutralizing antibody (NA) and siRNA targeting FGFR2c, whereas FGFR2b signaling was not inhibited. Moreover, the expression of marker genes related to EMT was induced by FGF2, and this expression was suppressed by the NA. These results suggested that branching morphogenesis in SGs is regulated by FGFR2c, in addition to FGFR2b. Interestingly, FGFR2c signaling also led to increased fgf10 expression, and this increase was suppressed by the NA. FGFR2c signaling regulates branching morphogenesis through the activation of FGFR2b signaling via increased FGF10 autocrine. These results provide new insight into the mechanisms by which crosstalk between FGFR2b and FGFR2c results in efficient branching morphogenesis.
authors.affiliation: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Minami
authors.initials: M
authors.lastname: Shibuya
authors.affiliation: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ikari
authors.affiliation: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: gs5603@dent.kyushu-u.ac.jp.
authors.forename: Goro
authors.initials: G
authors.lastname: Sugiyama
authors.affiliation: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ohyama
authors.affiliation: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Kumamaru
authors.affiliation: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Nagano
authors.affiliation: Maxillofacial Diagnostic and Surgical Sciences, Department of Oral and Maxillofacial Rehabilitation, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sugiura
authors.affiliation: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Kanemitsu
authors.initials: K
authors.lastname: Shirasuna
authors.affiliation: Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Mori
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000235:genetics*; D004847:Epithelial Cells / Q000378:metabolism; D051526:Fibroblast Growth Factor 10 / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009024:Morphogenesis / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D012469:Salivary Glands / Q000254:growth & development* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D020033:Protein Isoforms; D051497:Receptor, Fibroblast Growth Factor, Type 2
keywords: Branching morphogenesis; EMT; FGFR2b; FGFR2c; Salivary gland