title: Differential regulation of TIMP-1, -2, and -3 mRNA and protein expressions during mouse incisor development.
abstract: Tissue inhibitors of metalloproteinases (TIMPs) possess multiple functions, in addition to their matrix metalloproteinase (MMP) inhibitory activity. The continuously growing incisor of mouse possesses a stem cell compartment at the apical end of the epithelium (the apical loop) and thus provides an excellent tool to analyze the mechanisms of organogenesis and cytodifferentiation. To understand the functions of TIMPs in tooth development, we have analyzed the gene expression and protein localization of TIMP-1, -2, and -3 during mouse incisor development, from embryonic day 13 (E13) to postnatal day 3 (P3). TIMP-1 was present on the basement membrane during early developmental stages. At P2, TIMP-1 was strongly detected along the apical loop, transiently disappeared from the basement membrane in the cytodifferentiation zone, and later reappeared at the distal end of functional ameloblasts. Expression of TIMP-2 protein was restricted to the outer part of the apical loop throughout the examined stages. At P2, TIMP-2 was present on the basement membrane at the outer part of the apical loop. The dental follicle also expressed Timp-2, and the corresponding protein was abundant within the extracellular matrix. Timp-3 mRNA was highly expressed in the mesenchyme surrounding the apical loop. During matrix formation, Timp-3 was expressed by subodontoblasts, and the protein was detected in this layer and between odontoblasts. Distinct temporal and spatial expression patterns of TIMPs suggest divergent functions of these factors in incisor organogenesis.
authors.affiliation: Division of Cariology, Operative Dentistry and Endodontics, Department of Oral Health Science, Niigata University Graduate School of Medical and Dental Sciences, 5274, Niigata, Japan. nagako@dent.niigata-u.ac.jp
authors.forename: Nagako
authors.initials: N
authors.lastname: Yoshiba
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Yoshiba
authors.forename: Corinne
authors.initials: C
authors.lastname: Stoetzel
authors.forename: Fabienne
authors.initials: F
authors.lastname: Perrin-Schmitt
authors.forename: Yves
authors.initials: Y
authors.lastname: Cam
authors.forename: Jean Victor
authors.initials: JV
authors.lastname: Ruch
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hosoya
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Ozawa
authors.forename: Hervé
authors.initials: H
authors.lastname: Lesot
mesh_terms: D000818:Animals; D018507:Gene Expression Regulation, Developmental; D007180:Incisor / Q000196:embryology* / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D012333:RNA, Messenger / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism* / Q000502:physiology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism* / Q000502:physiology; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism* / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D019716:Tissue Inhibitor of Metalloproteinase-2