title: Interaction between fibronectin and β1 integrin is essential for tooth development.
abstract: The dental epithelium and extracellular matrix interact to ensure that cell growth and differentiation lead to the formation of teeth of appropriate size and quality. To determine the role of fibronectin in differentiation of the dental epithelium and tooth formation, we analyzed its expression in developing incisors. Fibronectin mRNA was expressed during the presecretory stage in developing dental epithelium, decreased in the secretory and early maturation stages, and then reappeared during the late maturation stage. The binding of dental epithelial cells derived from postnatal day-1 molars to a fibronectin-coated dish was inhibited by the RGD but not RAD peptide, and by a β1 integrin-neutralizing antibody, suggesting that fibronectin-β1 integrin interactions contribute to dental epithelial-cell binding. Because fibronectin and β1 integrin are highly expressed in the dental mesenchyme, it is difficult to determine precisely how their interactions influence dental epithelial differentiation in vivo. Therefore, we analyzed β1 integrin conditional knockout mice (Intβ1lox-/lox-/K14-Cre) and found that they exhibited partial enamel hypoplasia, and delayed eruption of molars and differentiation of ameloblasts, but not of odontoblasts. Furthermore, a cyst-like structure was observed during late ameloblast maturation. Dental epithelial cells from knockout mice did not bind to fibronectin, and induction of ameloblastin expression in these cells by neurotrophic factor-4 was inhibited by treatment with RGD peptide or a fibronectin siRNA, suggesting that the epithelial interaction between fibronectin and β1 integrin is important for ameloblast differentiation and enamel formation.
authors.affiliation: Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors.forename: Kan
authors.initials: K
authors.lastname: Saito
authors.affiliation: Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Fukumoto
authors.affiliation: Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Yamada
authors.affiliation: Pediatric Dentistry, St. Mary's Hospital, Kurume, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yuasa
authors.affiliation: Section of Orthodontics, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Yoshizaki
authors.affiliation: Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai, Japan; Department of Pediatric Dentistry, University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Iwamoto
authors.affiliation: Operative Dentistry, Department of Restorative Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Saito
authors.affiliation: Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukumoto
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002454:Cell Differentiation; D002460:Cell Line; D024141:Collagen Type IV / Q000378:metabolism; D003746:Dental Enamel Proteins / Q000378:metabolism; D004848:Epithelium / Q000254:growth & development / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D007180:Incisor / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008963:Molar / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051381:Rats
chemical_list: C490890:Ambn protein, mouse; D024141:Collagen Type IV; D003746:Dental Enamel Proteins; D005353:Fibronectins; D019012:Integrin beta1; C513277:Lamb1 protein, mouse; D007797:Laminin; D009414:Nerve Growth Factors; D048049:Extracellular Signal-Regulated MAP Kinases; C073922:neurotrophin 4
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