Tooth development is a complex schedule of cell division, differentiation, morphogenesis and tissue-specific extracellular matrix biomineralization. The major objective of this research project is to determine if locally produced growth factors, acting as autocrine and/or paracrine mediators, regulate dentine and enamel biomineralization. We propose to test the hypothesis that time and position-restricted growth factor expression regulates dentine and enamel biomineralization. A recently developed simple organ culture system devoid of exogenous serum or plasma supplementation provides a controlled model to test our hypothesis. The following specific aims are designed to test our hypothesis: (i) to identify and quantitate locally produced growth factor mRNAs and translation products during dental tissue biomineralization; (ii) to determine the timing and position of selected growth factor expression; (iii) to determine if selected exogenous growth factors down-regulate local transcription of growth factors; (iv) to determine if endocrine hormones (e.g. growth hormone) up-regulate locally produced growth factors and stimulate biomineralization; and (v) to determine the function(s) of selected growth factors in dentine and enamel biomineralization. Methods employed include microdissection of embryonic mouse molar tooth organs, organ culture using serumless and chemically-defined medium, mRNA phenotyping using RT-PCT, in situ hybridization, immunocytochemistry, microinjection, immunoperturbation and antisense assays, light and electron microscopy, electron diffraction assays, and computer-assisted three- dimensional reconstruction. These studies use embryonic, fetal and neonatal Swiss Webster strain mouse molar tooth organs.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
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Oral Biology and Medicine Subcommittee 1 (OBM)
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University of Southern California
Schools of Dentistry
Los Angeles
United States
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Caton, Javier; Bringas Jr, Pablo; Zeichner-David, Margarita (2005) IGFs increase enamel formation by inducing expression of enamel mineralizing specific genes. Arch Oral Biol 50:123-9
Takahashi, K; Yamane, A; Bringas, P et al. (1998) Induction of amelogenin and ameloblastin by insulin and insulin-like growth factors (IGF-I and IGF-II) during embryonic mouse tooth development in vitro. Connect Tissue Res 38:269-78;discussion 295-303
Slavkin, H C; Diekwisch, T G (1997) Molecular strategies of tooth enamel formation are highly conserved during vertebrate evolution. Ciba Found Symp 205:73-80; discussion 81-4
Slavkin, H C; Diekwisch, T (1996) Evolution in tooth developmental biology: of morphology and molecules. Anat Rec 245:131-50
Hu, J C; Zhang, C; Slavkin, H C (1995) The role of platelet-derived growth factor in the development of mouse molars. Int J Dev Biol 39:939-45
Diekwisch, T G; Berman, B J; Gentner, S et al. (1995) Initial enamel crystals are not spatially associated with mineralized dentine. Cell Tissue Res 279:149-67
Nakamura, M; Bringas Jr, P; Nanci, A et al. (1994) Translocation of enamel proteins from inner enamel epithelia to odontoblasts during mouse tooth development. Anat Rec 238:383-96
Shum, L; Sakakura, Y; Bringas Jr, P et al. (1993) EGF abrogation-induced fusilli-form dysmorphogenesis of Meckel's cartilage during embryonic mouse mandibular morphogenesis in vitro. Development 118:903-17
Diekwisch, T; David, S; Bringas Jr, P et al. (1993) Antisense inhibition of AMEL translation demonstrates supramolecular controls for enamel HAP crystal growth during embryonic mouse molar development. Development 117:471-82
Slavkin, H C (1993) Rieger syndrome revisited: experimental approaches using pharmacologic and antisense strategies to abrogate EGF and TGF-alpha functions resulting in dysmorphogenesis during embryonic mouse craniofacial morphogenesis. Am J Med Genet 47:689-97;discussion 687-8

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