title: Specific transforming growth factor-beta subtypes regulate embryonic mouse Meckel's cartilage and tooth development.
abstract: Members of the transforming growth factor-beta (TGF-beta) superfamily have emerged as critical regulators for cell growth and differentiation. Whereas the different TGF-beta subtypes are equipotent in the majority of biological assays using cell lines cultured in vitro, there are indications that in more complex systems involving epithelial-mesenchymal interactions, the TGF-beta subtypes differ in their biological activities. To test the hypothesis that TGF-beta subtypes specifically regulate either Meckel's cartilage or tooth morphogenesis, we designed experiments to compare loss of function effects of TGF-beta 1, TGF-beta 2, and TGF-beta 3 subtypes using a serumless, chemically defined medium to culture embryonic mouse E10 (42-44 somite pairs) mandibular explants. The major effect of loss of function resulting from abrogation of TGF-beta 1 using antisense treatment resulted in a 20% increase (P < 0.05) in chondrocyte number, a decrease in extracellular matrix, and dysmorphology of the rostral region of Meckel's cartilage. Exogenous TGF-beta 1 provided indistinguishable recovery to the normal phenotype. TGF-beta 2 antisense treatment produced a threefold enlargement (P < 0.05) of tooth organs and advanced their development to the cap stage. TGF-beta 2 provided recovery to the normal phenotype (e.g., reduced tooth size and development to the bud stage), whereas TGF-beta 1 or TGF-beta 3 polypeptides had no effect. TGF-beta 3 antisense treatment resulted in a reduction of approximately 15% in the length of Meckel's cartilage. We interpret these results to suggest that TGF-beta 1 functions to regulate the number of chondrogenic cells, the amount of extracellular matrix, and the rate of developmental assembly of the rostral to posterior segments in forming Meckel's cartilage. TGF-beta 2 appears to regulate tooth size and stage of development without affecting cartilage. TGF-beta 3 appears to regulate Meckel's cartilage size without altering tooth size or shape. The results are discussed in terms of the regulatory functions of the TGF-beta subtypes during embryonic craniofacial morphogenesis.
authors.affiliation: Center for Craniofacial Molecular Biology, School of Dentistry, University of Southern California, Los Angeles 90033.
authors.forename: Y
authors.initials: Y
authors.lastname: Chai
authors.forename: A
authors.initials: A
authors.lastname: Mah
authors.forename: C
authors.initials: C
authors.lastname: Crohin
authors.forename: S
authors.initials: S
authors.lastname: Groff
authors.forename: P
authors.initials: P
authors.lastname: Bringas
authors.forename: T
authors.initials: T
authors.lastname: Le
authors.forename: V
authors.initials: V
authors.lastname: Santos
authors.forename: H C
authors.initials: HC
authors.lastname: Slavkin
mesh_terms: D000818:Animals; D001483:Base Sequence; D002356:Cartilage / Q000196:embryology* / Q000254:growth & development; D046508:Culture Techniques; D005260:Female; D007150:Immunohistochemistry; D008334:Mandible / Q000196:embryology* / Q000254:growth & development; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis; D016376:Oligonucleotides, Antisense; D014070:Tooth / Q000196:embryology* / Q000254:growth & development; D016212:Transforming Growth Factor beta / Q000145:classification / Q000502:physiology*
chemical_list: D016376:Oligonucleotides, Antisense; D016212:Transforming Growth Factor beta