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Biomedical subjects

H C Slavkin

Publications and source records attributed to H C Slavkin.

At least 217 records · Page 12Linked to original sources
PubMed1983

Basal lamina persistence during epithelial-mesenchymal interactions in murine tooth development in vitro.

Numerous investigations have demonstrated the necessity of mesenchymal instruction for epithelial differentiation during epidermal organogenesis. In the specific case of tooth formation, cap-stage tooth organ mesenchyme instructs epithelial differentiation into ameloblasts with production of enamel extracellular matrix. The "instructive event" is presumed to be direct cell contact. Mesenchyme-mediated cell contact with adjacent epithelia is assumed to "instruct" epithelial differentiation into ameloblasts. If this were true, basal lamina removal and mesenchyme cell contact with epithelia would be prerequisites for epithelial cytodifferentiation and morphogenesis in the developing tooth system. To test this hypothesis, we designed experiments to evaluate basal lamina stability during epithelial differentiation into ameloblasts. Our studies utilized cap-stage murine molar tooth organs, a serumless and chemically defined medium (PYMS), metabolic isotopic labeling of basal lamina constituents, biochemical methods to analyze macromolecular stability throughout 10 days of organ culture in vitro, and immunological methods to localize the distribution of laminin and fibronectin. Our results indicate that (3H)glucosamine is incorporated into basement membranes present in Theiler stage 25 mandibular mouse molar tooth organ. At this stage, the isotope was incorporated into high molecular weight macromolecules. Specific enzyme methods coupled with electrophoresis and fluorography demonstrated that (3H)glucosamine was incorporated into proteoglycans containing chondroitin sulfates, dermatan sulfate, and hyaluronate. After 10 days in vitro the radiolabeled material remained localized in these same molecules, indicating stability of these constituents within basement membranes. Ultrastructural observations indicated that the basal lamina was not removed during ameloblast differentiation in vitro using PYMS medium. Laminin and fibronectin were localized in the basement membranes during cap stages and did not disappear during subsequent morphogenesis and differentiation. Mesenchymal cells appear to mediate epithelial differentiation in vitro using PYMS medium without a removal of the basal lamina.

Animals↗
PubMed1983

Selachian tooth development: I. Histogenesis, morphogenesis, and anatomical features in Squalus acanthias.

We have determined the general features of epithelial-mesenchymal interactions during fetal and mature adult stages of odontogenesis in the selachian spiny dogfish, Squalus acanthias. The general features of odontogenesis included the formation of an extended dental lamina, bud, cap, bell, and crown stages as identified and described using serial sections from fetal as well as adult specimens and light microscopy. Fetal and adult lengths, the rostrum-caudal fin distance, were correlated with the number of tooth rows and columns present in each specimen. This positional information and terminology was extremely valuable in attempting to acquire reproducible data for analyses. Whereas a number of histologic features of fetal and adult odontogenesis were comparable to those described in Mammalia, we found a number of epithelial-mesenchymal interaction characteristics unique to elasmobranch tooth development, including the persistence of the dental lamina in the adult stages, the coupling of cervical inner enamel epithelia between sequential stages of tooth formation, and the patterns of odontogenesis in the adult dentition.

Animals↗
PubMed1983

Selachian tooth development: III. Ultrastructural features of secretory amelogenesis in Squalus acanthias.

Ultrastructural features of secretory amelogenesis during selachian tooth development show several similarities to mammalian amelogenesis. However, the following critical differences were noticed: 1) subcellular organelles associated with merocrine-type protein synthesis and secretion were located in both the infranuclear as well as supranuclear regions of the selachian ameloblasts; 2) no evidence for Tomes process formation was found; 3) the basal lamina was not removed during epithelial differentiation into ameloblasts in the selachian model, and the structural features of the basal lamina were significantly altered during amelogenesis in rows III, IV, and VI; and 4) no dentine-enameloid junction was detected. It is suggested that enameloid is an extracellular matrix which is derived from the selachian inner enamel epithelium and appears to be secreted from both the lateral and apical surfaces of ameloblasts.

Amelogenesis↗
PubMed1982

Initiation of quail and mouse mandibular chondrogenesis and osteogenesis in a serumless, chemically-defined medium.

To evaluate the requirement of vascular and/or neurotrophic-derived factors on determination and differentiation of chondrogenic and osteogenic phenotypes, early embryonic quail and mouse mandibular processes were cultured using a modified Trowell method in a serumless, chemically-defined medium for 10 days. Quail HH stage 22 and mouse Theiler stage 16 mandibular processes formed cartilage and produced osteoid under these experimental conditions. Chondrogenic and osteogenic phenotypes were expressed without serum or other exogenous growth-promoting influences.

Animals↗
PubMed1982

Maternal influences on congenital craniofacial malformations.

Congenital craniofacial malformations represent an extremely complex biomedical problem area. The complexity includes early detection, diagnosis, treatment, habilitation, and, of course, prevention. The genetic and environmental issues which appear to interact and result in congenital malformations are becoming better understood. Rapid advances in mouse and human immunogenetics indicate several possible explanations as to why some individuals acquire certain birth defects whereas other individuals do not express congenital malformations. Recent discoveries concerning the major histocompatibility complex (MHC) and associations with a number of human malformations have stimulated interesting speculations concerning genetic and environmental factors which might be responsible for predispositions to congenital malformations. Of particular interest is the possible function of the major histocompatibility complex of the mother during early stages of embryogenesis and how this assembly of genes may confer susceptibility to environmentally induced birth defects in mouse and human reproduction.

Abnormalities, Drug-Induced↗
PubMed1982

Enamel gene products during murine amelogenesis in vivo and in vitro.

Epithelial-mesenchymal interactions regulate determination and differentiation of amelogenesis. Our attention has focused on identification of ameloblast gene products, the regulation of enamel mRNA synthesis, and subsequent translation into enamel proteins in vivo and in vitro. Enamel proteins are the most abundant gene products synthesized in fully-differentiated ameloblasts. Our experimental strategy has been to isolate major proteins, produce antibodies, localize enamel protein antigens during tooth development in vivo as well as in vitro (using serumless, chemically-defined medium), develop an immunoprecipitation assay, isolate poly(A)-products in a cell-free translation system, and then initiate molecular cloning of the corresponding murine enamel gene(s). The major murine enamel mRNA appears to code for a predominant polypeptide of approximately 20,000 MW. Inner-enamel epithelial cells differentiate into ameloblasts, and synthesize and secrete enamel proteins within six d when cap-stage molar tooth organs are cultured in serumless, chemically-defined medium. The regulation of epithelial differentiation under these experimental conditions indicates that epithelial-mesenchymal interactions determine and maintian ameloblast differentiation in vitro.

Ameloblasts↗
PubMed1982

Epithelial-derived basal lamina regulation of mesenchymal cell differentiation.

The mechanisms by which epithelial-mesenchymal interactions result in differentiation are not known. A number of recombinations between vertebrate tissues associated with epidermal organs (e.g. skin, feather, mammary gland, salivary gland, tooth organ) indicate that regional mesenchymal specificity is instructive for determination and differentiation of epithelial phenotypes. In epidermal organs within which mesenchyme becomes determined and differentiates into a unique phenotype, such as during tooth organogenesis and odontoblast differentiation. Does the epithelial-derived basal lamina regulate mesenchymal differentiation into odontoblasts and the expression of dentine extracellular matrix? Experiments were designed to test the hypothesis that murine or avian epithelial-derived basal lamina possess information which is instructive for determined dental mesenchyme to differentiate into odontoblasts. The strategy was to examine homologous and heterologous tissue recombinants between Theiler stage 25 C57BL/6 molar tooth organs and Hamburger-Hamilton equivalent stage 22-26 Japanese Pharoah quail mandibular processes. Trypsin-dissociated molar epithelium and mesenchyme, reconstituted, secreted a basal lamina within 8 hours and mesenchyme differentiated into odontoblasts and formed dentine matrix within 3 days. Isolated trypsin-dissociated mesenchyme did not differentiate in vitro, whereas heterologous recombinants between odontogenic mesenchyma and quail epithelia resulted in odontoblasts and dentine production. Mouse tooth or quail mandibular epithelia served to regulate odontogenic mesenchyme differentiation. EDTA-dissociated mouse molar mesenchyme, in the absence of epithelium but with adherent basal lamina, routinely differentiated into odontoblasts. Control tooth organs routinely formed both dentine and enamel extracellular matrices within 7-10 days in our serumless, chemically-defined organ culture system. Regulation of determined mesenchymal cells to differentiate into functional and highly specialized odontoblasts appears to be mediated by epithelial-derived basal lamina and is not species or organ-specific.

Animals↗
PubMed1982

Combinatorial process for extracellular matrix influences on gene expression: a hypothesis.

The extracellular matrix (ECM) has a number of influences on gene expression during growth and development. Cellular and tissue interactions among similar and dissimilar cell types result in the production of complex and fascinating extracellular matrices throughout development. This paper presents a hypothesis that will emphasize those examples in which the extracellular matrix mediates de novo gene expression termed "determination" of a unique phenotype. It will be found that a number of gene families within the eucaryotic genome can be preferentially activated during the course of differentiation-specific protein expression. Results from a number of laboratories illustrate that close-range and/or short-range cell-cell interactions invoke preferential differentiation-specific protein synthesis and accumulation during embryogenesis. This discussion will highlight how the extracellular matrix microenvironment of a particular population of cells invokes irreversible, differentiation-specific gene expression. Recent advances in the isolation and characterization of a large number of different extracellular matrix macromolecules (eg various types of collagens, fibronectin, chondronectin, osteonectin, laminin, proteoglycans, enamel protein) now suggest a renewed interest in this problem area, and also the promise for significant breakthroughs in the near future. The combinatorial hypothesis for extracellular matrix influences on gene expression states that changing, rearranging, or altering the macromolecular constituents within ECM results in a myriad diversity in developmental instructions. The hypothesis predicts that no individual morphogen is required.

Cell Communication↗
PubMed1981

Corticosteroid-induced cleft lip in mice: a teratologic, topographic, and histologic investigation.

Unlike cleft palate, relatively few teratogens have been found to induce cleft lip in mice. The present study was designed to assess the teratologic, topographic (SEM), and histologic effects on lip morphogenesis following the administration of triamcinolone hexacetonide on the eighth day of gestation. The frequency of cleft lip in treated A/J mice was found to be more than three times greater than the spontaneous frequency in untreated controls. Comparable studies with other murine strains suggest no association between the cleft lip response and either a maternal effect or the H-2 complex. Affected A/J embryos showed a severe reduction in the size of the lateral nasal processes; affected embryos also demonstrated localized cell type-specific alterations, particularly in the epithelia and at the interface between epithelium and mesenchyme.

Abnormalities, Drug-Induced↗
PubMed1981

The association of H-2 haplotype with implantation, survival, and growth of murine embryos.

Using three congenic strains, C57BL/10Sn(H-2b), B10.A/SnSg(H-2a), and B10.D2/nSn(H-2d), we sought to investigate the possible association of H-2 haplotype with the number of implants, fetal survival, and fetal weight, as well as to analyze the possible effects of hybrid vigor and maternal-fetal histoincompatibility in primigravidae mice. The results of this study indicate a significant association between genes at or near the H-2 complex and both fetal loss and fetal weight, but not the number of implants. Haplotype variation accounted for 14 percent of the variation in fetal loss and 20 percent of the variation in fetal weight. With the exception of fetal loss, there was no evidence of a maternal effect. There was also no clear evidence of hybrid vigor or histoincompatibility effects for any of the three variables studied. In summary, the data suggests that particular allelic variants at or near the H-2 complex confer some selective advantage as measured by differential fetal survival and fetal growth.

Animals↗
PubMed1981

Corticosteroid-induced cleft palate in mice and H-2 haplotype: maternal and embryonic effects.

This report confirms and expands on the original preliminary observations made by Bonner and Slavkin that corticosteroid-induced cleft palate in mice is associated with H-2 haplotype. Using three congenic strains, B10, B10.A, and B10.D2, our studies demonstrate that B10.A (H-2a) is most susceptible and B10.D2(H-2d) is least susceptible, B10(H-2b) being intermediate. Variation in fetal loss among strains accounts for less than 1 percent of the variation in cleft-palate frequency among strains; variation in H-2 haplotype, however, accounts for more than 60 percent of the variation in cleft-palate frequency. With regard to all possible reciprocal F1 hybrids, our results indicate that while there is a significant maternal effect, maternal haplotype can account for only 11 percent of the variation in cleft-palate frequency among crosses. Embryonic haplotype accounts for 17 percent of the variation, which is indicative of an important embryonic effect. Finally, our studies suggest that susceptibility to corticosteroid-induced cleft palate is associated with the K end of the H-2 complex.

Adrenal Cortex Hormones↗