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S Vainio

Publications and source records attributed to S Vainio.

At least 37 records · Page 2Linked to original sources
PubMed1993

Identification of BMP-4 as a signal mediating secondary induction between epithelial and mesenchymal tissues during early tooth development.

Growth factor-mediated signaling has been implicated in the regulation of epithelial-mesenchymal interactions during organogenesis. Bone morphogenetic protein 4 (BMP-4), a member of the transforming growth factor beta superfamily, is expressed in the presumptive dental epithelium at the initiation of tooth development. Subsequently, epithelial signaling leads to mesenchymal induction of BMP-4 expression. To address the role of this factor, BMP-4-releasing agarose beads were added to dental mesenchyme in culture. These beads induced a translucent mesenchymal zone similar to that induced by dental epithelium. Moreover, three transcription factors (Msx-1, Msx-2, and Egr-1) whose expression is governed by epithelial signaling were induced in response to BMP-4. In addition, BMP-4 induced its own mesenchymal expression. These findings support the hypothesis that BMP-4 mediates epithelial-mesenchymal interactions during early tooth development.

Animals↗
PubMed1993

Transient expression of type III collagen by odontoblasts: developmental changes in the distribution of pro-alpha 1(III) and pro-alpha 1(I) collagen mRNAs in dental tissues.

The expression of pro-alpha 1(III) and pro-alpha 1(I) collagen mRNAs in mouse and human dental tissues during tooth development and after its completion was analyzed by in situ hybridization, with use of [35S]-labeled RNA probes. The expression of pro-alpha 1(III) mRNA was also compared to that of the protein product, as localized by immunostaining with polyclonal antibodies to type III collagen and the N-terminal propeptide of type III procollagen. Contrary to many previous reports, our results suggest that odontoblasts express type III collagen. While pro-alpha 1(III) transcripts were less intensely expressed in odontoblasts than pro-alpha 1(I) transcripts, the amounts of both mRNAs increased in odontoblasts with progressing dentin formation, and decreased toward its completion. In contrast to pro-alpha 1(III) mRNA, pro-alpha 1(I) mRNA was still detectable in odontoblasts of fully developed teeth. Type III collagen immunoreactivity was observed in the early predentin, and again in predentin toward the completion of dentinogenesis, when mRNA was no longer detected. Also in the pulp, the protein product, unlike pro-alpha 1(III) mRNA, was relatively strongly expressed. Hence, these immunostaining patterns were inversely related to the expression of pro-alpha 1(III) mRNA, suggesting accumulation of the protein. The mesenchymal cells, when condensed in the region of the future mandibular bone, expressed pro-alpha 1(III) mRNA intensely, whereas osteoblasts expressed pro-alpha 1(I) but not pro-alpha 1(III) transcripts strongly. Cell type- and developmental stage-related differences in the expression of the two mRNAs suggest that type I/type III collagen ratio influences the structure of dental tissues.

Aging↗
PubMed1993

A chondroitin sulfate epitope in mammalian dental pulp and its developmental expression in mouse dental papilla.

The molecular specificity of the dental papilla of a bell-stage tooth was studied by production of dental-papilla-reactive monoclonal antibodies (Mabs). One of the Mabs, designated 7C5, recognized an epitope present in glycosaminoglycan. Several lines of evidence suggested that the 7C5-epitope consists of chondroitin 6-sulfate. The Mab did not react with mouse dental epithelium, but reacted uniformly with mesenchymal tissue in the mandibular process and accumulated in the dental sac and in the papilla of bell-stage tooth germs. The 7C5-staining was lost from the differentiating odontoblasts, while the staining in the molar tooth papilla was accumulated in the subodontoblastic layer. In the developing mouse incisor, the 7C5-epitope was restricted to the lingual-posterior area. The 7C5-epitope was also present in pulpal tissue and predentin of different types of teeth of various mammalian species, including man, sheep, swine, and rat. Collagenase pre-treatment of tissue sections abolished the bulk of the 7C5-reactivity in peridental mesenchyme during embryonic stages while leaving the staining of the dental papilla intact. In newborn and adult teeth, collagenase also impaired the reactivity in the pulp except for the subodontoblastic layer. This suggests the existence of different subpopulations of the 7C5-epitope containing proteoglycans in dental papilla and pulp. A high-molecular-weight proteoglycan, sensitive to chondroitinase ABC but not to heparinase or heparitinase, was immunoprecipitated by 7C5 from extracts of bell-stage mouse tooth germs. We suggest that the evolutionary conservation of chondroitin 6-sulfate in the dental pulp reflects its properties as non-terminally differentiated tissue and perhaps the retention of a potential to differentiate to odontoblasts.

Animals↗
PubMed1993

Epithelial-mesenchymal interactions are required for msx 1 and msx 2 gene expression in the developing murine molar tooth.

Duplication of the msh-like homeobox gene of Drosophila may be related to the evolution of the vertebrate head. The murine homologues of this gene, msx 1 and msx 2 are expressed in the developing craniofacial complex including the branchial arches, especially in regions of epithelial-mesenchymal organogenesis including the developing tooth. By performing in vitro recombination experiments using homochronic dental and non-dental epithelial and mesenchymal tissues from E10 to E18 mouse embryos, we have found that the maintenance of homeobox gene expression in the tooth is dependent upon tissue interactions. In homotypic recombinants, dental-type tissue interactions occur, leading to expression of both genes in a manner similar to that seen during in vivo development. msx 1 is expressed exclusively in mesenchyme, both in the dental papilla and follicle. msx 2 is expressed in the dental epithelium and only in the mesenchyme of the dental papilla. In heterotypic recombinants, the dental epithelium is able to induce msx 1 expression in non-dental mesenchyme, this potential being lost at the bell stage. In these recombinants msx 2 was induced by presumptive dental epithelium prior to the bud stage but not thereafter. The expression of msx 1 and msx 2 in dental mesenchyme requires the presence of epithelium until the early bell stage. However, whereas non-dental, oral epithelium is capable of maintaining expression of msx 1 in dental mesenchyme throughout tooth development, induction of msx 2 was temporally restricted suggesting regulation by a specific epithelial-mesenchymal interaction related to the inductive events of tooth formation. msx 1 and msx 2, as putative transcription factors, may play a role in regulating the expression of other genes during tooth formation. We conclude that expression of msx 1 in jaw mesenchyme requires a non-specific epithelial signal, whereas msx 2 expression in either epithelium or mesenchyme requires reciprocal interactions between specialized dental cell populations.

Animals↗
PubMed1992

Coordinated induction of cell proliferation and syndecan expression in dental mesenchyme by epithelium: evidence for diffusible signals.

Epithelial-mesenchymal interactions induce the expression of syndecan, a cell surface proteoglycan, and tenascin, an extracellular matrix glycoprotein in the mesenchymal component of many organ rudiments including the tooth. Experimental recombination cultures of early dental epithelium and mesenchyme were analysed by double immunostaining to compare the distribution of syndecan, tenascin, and proliferating cells (BrdU incorporation) in the induced dental mesenchyme. After 5-9 hr in culture expression of syndecan and tenascin as well as an increase in BrdU incorporation were evident in the mesenchymal cells adjacent to the epithelium and the positive area enlarged with time. Syndecan and tenascin were colocalized only partially in some explants. The expression of syndecan and tenascin in the recombinants correlates with their stage-dependent expression pattern during early tooth development in vivo (Vainio and Thesleff, 1992). The area of increased cell proliferation in the mesenchyme correlated closely with syndecan expression. In none of the explants was increased BrdU incorporation observed in syndecan negative areas. Epithelium induced also condensation of the mesenchymal cells. Induction and spread of the syndecan-positive zone in the dental mesenchyme required close and continuous contact with the epithelium. The mechanism by which the induction of syndecan expression spreads in the mesenchyme was studied in rat-mouse interspecies recombination cultures, using syndecan antibodies that recognize mouse but not rat syndecan. The rat mesenchyme and epithelium were first cultured in contact for 24 hr. Then the epithelium was removed and freshly dissected, "uninduced" mouse mesenchyme was placed in contact with different aspects of the rat mesenchyme. The rat mesenchymal cells that had located next to the epithelial tissue stimulated syndecan expression in adjacent mouse mesenchyme. The induction potential was gradually lost toward the periphery of the rat mesenchyme. Based on these findings we suggest that diffusible signal molecules mediate the spread of syndecan induction in the mesenchyme and that syndecan plays a role in the regulation of cell proliferation.

Animals↗
PubMed1992

Transient expression of syndecan in mesenchymal cell aggregates of the embryonic kidney.

Induction of the embryonic kidney mesenchyme is followed by formation of cell aggregates which subsequently transform into epithelial tubules. Syndecan, which binds various matrix components and growth factors, is a candidate molecule to be involved in this process. We have analyzed the changes in the expression of syndecan during tubule morphogenesis by using in situ hybridization and slot-blot analysis. The expression pattern of syndecan was compared with the distribution of cell proliferation analyzed by immunohistochemistry. Furthermore, the expression of syndecan during formation of the pretubular aggregates was studied in hanging-drop cultures of experimentally induced mesenchymal cells. Syndecan mRNA was expressed in the metanephric mesenchyme prior to induction, was intensely present during formation of the pretubular cell aggregates, but was lost during maturation of the nephron. Slot-blot analyses of the kidney mesenchymes (11-day kidney) cultured in a transfilter situation with a heterotypic inductor tissue that triggers a complete tubulogenic program in the nephric mesenchyme during the first 24 hr suggested the presence of syndecan mRNA in the uninduced mesenchymes with no change during induction. Expression of mRNA was stimulated later (13-day kidney) followed by subsequent decrease. Immunoisolation of sulfate-labeled syndecan, however, revealed a marked stimulation in the induced kidney mesenchyme during the first 24-hr inductive period when the DNA level still remained constant. In hanging-drop cultures where either induced or uninduced mesenchymal cells were dissociated and reaggregated, syndecan was detected only in the induced and aggregating mesenchymal cells. Double-immunostaining demonstrated a close correlation between syndecan expression and cell proliferation analyzed by bromodeoxyuridine incorporation. Thus, it appears that syndecan expression in the mesenchyme is initially induced post-transcriptionally and later during differentiation at the mRNA level. Syndecan may have a dual function during early kidney morphogenesis; it may be involved in cell aggregation through its adhesive properties, and it may contribute to proliferation of the induced mesenchymal cells by binding growth factors.

Animals↗
PubMed1992

Transient and recurrent expression of the Egr-1 gene in epithelial and mesenchymal cells during tooth morphogenesis suggests involvement in tissue interactions and in determination of cell fate.

We have analyzed the expression of early growth response gene (Egr-1) by mRNA in situ hybridization during mouse embryonic tooth development and in experimental recombinations of dental epithelium and mesenchyme. Egr-1 was transiently and recurrently expressed both in epithelial and mesenchymal cells starting from day 13 of gestation and up to 4 days after birth. The expression correlated with developmental transition points of dental mesenchymal and epithelial cells suggesting a role for Egr-1 in sequential determination and differentiation of cells. In recombination cultures of early dental epithelium and mesenchyme Egr-1 RNA was localized at the epithelial-mesenchymal interface in mesenchymal cells, and in two cases also in epithelial cells. These data indicate that Egr-1 expression may be regulated by epithelial-mesenchymal interactions when they are specific enough to initiate differentiation. We have also analyzed by in situ hybridization whether Wilms' tumour-1 gene (wt-1) is expressed in the developing tooth as it was proposed on the bases of in vitro studies that it may inhibit Egr-1 expression. No wt-1 expression was detected at any stage of tooth development showing that wt-1 is not obligatory for regulation of Egr-1 expression.

Animals↗
PubMed1992

Sequential induction of syndecan, tenascin and cell proliferation associated with mesenchymal cell condensation during early tooth development.

The cell surface proteoglycan, syndecan, and the extracellular matrix glycoprotein, tenascin, are expressed in the mesenchyme during early development of many organs. We have studied the expression patterns of syndecan and tenascin during initiation of tooth development and in association with mesenchymal cell condensation and compared these with cell proliferation. Syndecan, tenascin and bromodeoxyuridine (BrdU) incorporation were localized by triple-labelling immunohistochemistry in serial sections of molar tooth germs of mouse embryos. Prior to formation of the epithelial tooth bud, syndecan accumulated in the mesenchymal cells which underlie the presumptive dental epithelium, but tenascin was not detected at this stage. Tenascin appeared during initiation of the epithelial down-growth at the lingual aspect of the tooth germ. During subsequent formation of the epithelial bud, at the late bud stage, syndecan and tenascin became exactly colocalized in the condensed mesenchyme which was clearly demarcated from other jaw mesenchyme. The expression of syndecan and tenascin was accompanied by rapid cell proliferation as indicated by marked BrdU incorporation. When development advanced to the cap stage, syndecan staining intensity in the dental papilla mesenchyme increased further whereas tenascin became reduced. In conclusion, the results demonstrate that the expression patterns of syndecan and tenascin overlap transiently during the period of mesenchymal cell condensation and that this is accompanied by cell proliferation. Syndecan and tenascin may play a role in growth control and in compartmentalization of the dental mesenchymal cells in the condensate.

Animals↗
PubMed1992

Expression of type I collagen pro-alpha 2 chain mRNA in adult human permanent teeth as revealed by in situ hybridization.

The expression of the gene COL1A2, coding for the pro-alpha 2 chain of type I pro-collagen, was analyzed in fully developed human permanent teeth. The teeth were fixed with formalin, demineralized with EDTA for about ten weeks, and embedded in paraffin. Pro-alpha 2(I) mRNA was localized in the sections by in situ hybridization, with use of [35S)]-labeled single-stranded RNA probes. The amount of mRNA for pro-alpha 2(I) collagen chain, as indicated by the relative densities of silver grains and the grain counts per cell in autoradiography, was high in odontoblasts, whereas in pulpal fibroblasts it was low. High levels of pro-alpha 2(I)mRNA expression were also present in those odontoblasts which had elaborated new dentin matrix in response to dental caries. Expression in the periodontal ligament, including the cementoblast layer, was slightly stronger than that in odontoblasts. The intense expression of pro-alpha 2(I) mRNA in odontoblasts of adult teeth suggests that even after the completion of primary dentin formation, they continue to synthesize heterotrimeric type I collagen molecules. Cell type-specific differences in the expression of pro-alpha 2(I) mRNA imply that type I collagen probably plays a major role in the regulation of the structure and function of dental tissues. Finally, in situ hybridization enabled pro-alpha 2(I) collagen mRNA to be detected in tissue sections even after prolonged demineralization, and thus it proved to be a valuable technique for analysis of gene expression in adult dental tissues, as shown here for COL1A2.

Adult↗
PubMed1991

Syndecan from embryonic tooth mesenchyme binds tenascin.

Syndecan is a cell surface heparan sulfate-rich proteoglycan found on various epithelial cells but also in some embryonic mesenchymal tissues. We have immunoisolated syndecan from embryonic tooth mesenchyme that appeared as a 250-300-kDa molecule (Kav = 0.3 in Sepharose 4B), containing only heparan sulfate side chains (Mr = 35,000). Northern analysis of whole tooth germs and tooth mesenchymes also revealed high expression of syndecan mRNAs (2.6 and 3.4 kilobases). In the binding assay utilizing nitrocellulose as a solid phase to immobilize matrix molecules, syndecan immunoisolated from tooth mesenchyme revealed binding to tenascin, and this interaction was shown to be mediated via heparan sulfate side chains. In contrast, syndecan from mouse mammary epithelial cells showed only weak interaction with tenascin. We propose that syndecan and tenascin may represent interactions of a cell surface receptor and a matrix ligand involved in mesenchymal cell condensation and differentiation during early organogenesis.

Animals↗
PubMed1991

Expression of syndecan gene is induced early, is transient, and correlates with changes in mesenchymal cell proliferation during tooth organogenesis.

Syndecan is an integral cell surface proteoglycan which contains an extracellular matrix-binding domain and a cytoskeleton-associated domain and may therefore transfer changes in the extracellular environment to cellular behavior. Changes in syndecan gene expression during embryonic and early postnatal mouse tooth development were analyzed by in situ hybridization and compared with the distribution of syndecan core protein and cell proliferation studied by immunohistochemistry. Syndecan RNA became accumulated in the condensing mesenchymal cells around the invaginating epithelial tooth bud during early development, and this accumulation became more intense when morphogenesis advanced to the cap stage. During the bell stage, when the cuspal pattern of the tooth is established, syndecan transcripts were lost, and RNA was not detected in the terminally differentiated or postmitotic odontoblasts. In the epithelium, syndecan RNA was intensely expressed in the invaginating epithelial bud, but the expression was reduced during the cap and bell stages. However, local stimulation in syndecan gene expression was observed in the epithelial preameloblasts immediately preceding their terminal differentiation into ameloblasts, which was accompanied by a complete loss of transcripts. There was a close correlation between the changes in syndecan transcripts and the distribution of syndecan core protein. Furthermore, analysis of cell proliferation by immunohistochemical detection of BrdU incorporation revealed that in the mesenchyme, but not in the epithelium, syndecan was intensely expressed by proliferating cells. The analysis of mRNA by Northern blot indicated that the transcripts in mesenchymal and epithelial cells were of similar size. In the slot-blot analysis the changes in syndecan transcripts correlated with the overall changes observed in the in situ hybridization analysis. The role of tissue interactions in the regulation of the syndecan gene was studied by using tissue recombination cultures of separated epithelial and mesenchymal components of the early tooth germ. The in situ hybridization and Northern blot analysis of these explants showed that the expression was increased in the mesenchyme cultured in contact with the epithelium. Our results indicate that syndecan gene expression in the embryonic tooth mesenchyme is induced by epithelial-mesenchymal interactions and thereafter expressed stage-dependently and transiently by the differentiating cells during organogenesis. The association of syndecan expression with mesenchymal cell proliferation raises the possibility that, in addition to behaving as a matrix receptor, syndecan may have a role in controlling growth and that syndecan may have different functions in epithelial and mesenchymal cells.

Animals↗
PubMed1991

Induced expression of syndecan in healing wounds.

We have studied the expression of an integral cell surface proteoglycan, syndecan, during the healing of cutaneous wounds, using immunohistochemical and in situ hybridization methods. In normal mouse skin, both syndecan antigen and mRNA were found to be expressed exclusively by epidermal and hair follicle cells. After incision and subsequent suturing, remarkably increased amounts of syndecan on the cell surfaces of migrating and proliferating epidermal cells and on hair follicle cells adjacent to wound margins were noted. This increased syndecan expression was shown to be a consequence of greater amounts of syndecan mRNA. Induction was observed already 1 d after wounding, was most significant at the time of intense cell proliferation, and was still observable 14 d after incision. The migrating cells of the leading edge of the epithelium also showed enhanced syndecan expression, although clearly less than that seen in the proliferating epithelium. The merging epithelial cells at the site of incision showed little or no syndecan expression; increased syndecan expression, however, was detected during later epithelial stratification. When wounds were left unsutured, in situ hybridization experiments also revealed scattered syndecan-positive signals in the granulation tissue near the migrating epidermal sheet. By immunohistochemical analysis, positive staining in granulation tissue was observed around vascular endothelial cells in a subpopulation of growing capillaries. Induction of syndecan in granulation tissue both at the protein and mRNA levels was temporally and spatially highly restricted. Granulation tissue, which formed in viscose cellulose sponge cylinders placed under the skin of rats, was also found to produce 3.4 and 2.6 kb mRNA species of syndecan similar to that observed in the normal murine mammary epithelial cell line, NMuMG. These results suggest that syndecan may have a unique and important role as a cell adhesion and a growth factor-binding molecule not only during embryogenesis but also during tissue regeneration in mature tissues.

Animals↗
PubMed1991

Associations between transforming growth factor beta 1 RNA expression and epithelial-mesenchymal interactions during tooth morphogenesis.

We have studied the expression of transforming growth factor beta-1 (TGF-beta 1) RNA during mouse tooth development, using in situ hybridization and experimental tissue recombinations. Analysis of the serial sections revealed the appearance of local expression of TGF-beta 1 RNA in the dental epithelium at bud-staged teeth (13-day embryos). Just before transition to the cap stage, TGF-beta 1 RNA expression rapidly increased in the epithelial bud, and it also extended to the condensed dental mesenchyme. At cap stage (14- and 15-day embryos), there was an intense expression of TGF-beta 1 RNA in the morphologically active cervical loops of the dental epithelium. During early bell stage (16- and 17-day embryos), TGF-beta 1 RNA expression was detected in the inner enamel epithelium where it subsequently almost disappeared (18-day embryos). After birth TGF-beta 1 transcripts transiently appeared in these cells when they were differentiating into ameloblasts (1-day mice). The transcripts were lost from the ameloblasts when they became secretory (4-day mice), but the expression continued in ameloblasts in enamel-free areas. Transient expression of TGF-beta 1 RNA was also detected in epithelial stratum intermedium cells at the time of ameloblast differentiation. In the mesenchyme, TGF-beta 1 RNA was not detected during bell stage until it appeared in differentiated odontoblasts (18-day embryos). The secretory odontoblasts continued to express TGF-beta 1 RNA at all stages studied including the odontoblasts of incisor roots. Analysis of the distribution of bromodeoxyuridine (BrdU) incorporation indicated apparent correlations between TGF-beta 1 RNA expression and cell proliferation at the bud and cap stages but not at later stages of tooth development. Tissue recombination experiments of bud-staged (13-day embryos) dental and non-dental tissues showed that tooth epithelium, when cultured together with tooth mesenchyme, expressed TGF-beta 1 RNA. When the tooth epithelium was combined with non-dental jaw mesenchyme, TGF-beta 1 transcripts were not expressed. However, TGF-beta 1 RNA expression was seen in oral epithelium cultured with dental mesenchyme, while no expression of TGF-beta 1 transcripts was seen in the oral epithelium during normal development. Thus, TGF-beta 1 RNA expression seems to be regulated by epithelial-mesenchymal interactions.

Animals↗
PubMed1991

Advances in histological methods open up new perspectives for craniofacial growth research.

Changes in the tissue architecture and composition which accompany growth and development have traditionally been mapped using histological methods. The modern technology now offers new possibilities which can be used in connection with light microscopy and electron microscopy. These techniques, particularly immunohistochemistry and in situ hybridization allow studies on spatial and temporal changes in molecular patterns of substances during tissue organization and cell differentiation. In this paper, we describe the principles of immunohistology, autoradiography, and in situ hybridization, and review our recent studies in which we have applied such methods to assess craniofacial development. We have used autoradiography to localize cell proliferation and epidermal growth factor (EGF) receptors in the developing mandibular condyle. We have also used immunohistochemistry to localize the extracellular matrix component, tenascin, in differentiating chondrocytes of the mandibular condyle, employing specific antibodies. In studies on the odontogenic potential of dental papilla mesenchyme, we have used hybridoma technology, and produced monoclonal antibodies against dental papilla mesenchyme. Most recently, we have used in situ hybridization, which allows detection of gene expression in tissue sections to localize transcripts of a fibroblast-growth-factor related gene (Int-2 proto-oncogene) in developing teeth. In future, successful combination of such new histological methods and traditional experimental procedures can be expected to produce new answers to the questions about the regulation of craniofacial growth.

Facial Bones↗
PubMed1990

Molecular changes during determination and differentiation of the dental mesenchymal cell lineage.

The lineage of dental mesenchymal cells originates in the cranial neural crest, and after sequential determination and differentiation, gives rise to all structures of the tooth and its supporting tissues, except the enamel. Reciprocal interactions between the epithelial and mesenchymal tissues are conceivably the most important regulators of dental mesenchymal cell differentiation. The molecular mechanisms of this epigenetic regulation are not known at present. In order to examine the mechanisms of regulation of gene expression in the lineage of dental mesenchymal cells, information is needed on the molecular changes that accompany advancing differentiation. By using the molar tooth germ of mouse embryos as a model system, the changes in the expression of some molecules have been analysed by immunohistological localization and in situ hybridization, and the roles of tissue interactions in this process examined. This has shown that syndecan, a recently characterized cell surface proteoglycan, and tenascin, a matrix glycoprotein, appear in the condensing dental mesenchyme during the bud stage of tooth development. During the cap stage, dental mesenchyme is characterized by continued intense expression of syndecan, but this is lost during terminal differentiation of odontoblasts. Tenascin and syndecan may mediate cell-matrix interactions during condensation of dental mesenchymal cells. Expression of the Int-2 proto-oncogene, coding for a fibroblast growth factor-related molecule, can be detected by in situ hybridization in dental mesenchyme at the cap stage. This expression persists in cuspal mesenchyme at the bell stage but is lost from odontoblasts and from pulpal mesenchyme at progressive stages of tooth development. The advancement of tooth morphogenesis from cap to bell stage is accompanied by expression of alkaline phosphatase in the cuspal mesenchyme. Also tenascin, which is only weakly expressed during the cap stage, appears in the cuspal areas and shows codistribution with alkaline phosphatase. These observations indicate that the sequential determination and differentiation of the dental mesenchymal cells are characterized by a cascade of specific molecular changes. The cell surface proteoglycan syndecan and the Int-2 proto-oncogene are specific and transient markers of early dental mesenchymal cell differentiation. This information allows studies on the mechanisms of developmental regulation. These experimental tissue recombination studies indicate that the expression of syndecan and tenascin in the early dental mesenchyme is induced by the presumptive dental epithelium.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Epithelial-mesenchymal interactions regulate the stage-specific expression of a cell surface proteoglycan, syndecan, in the developing kidney.

Morphogenesis of the kidney is regulated by reciprocal tissue interactions between the epithelial ureter bud and the metanephric mesenchyme. The differentiation of the kidney involves profound changes in the extracellular matrix, and therefore matrix receptors may have an important role in this process. We studied the expression of syndecan, a cell surface proteoglycan acting as a receptor for interstitial matrix materials, by using a monoclonal antibody against the core protein of the molecule. Syndecan was not detected in the uninduced metanephric mesenchyme. During the formation of the ureter bud from the Wolffian duct, syndecan appeared in the mesenchymal cells around the invaginating bud. Simultaneously with the first branching of the ureter bud, the whole nephric mesenchyme became syndecan positive, but a 3- to 10-cell-thick layer around the branching ureter bud, representing the presumptive tubular cells, was most intensely stained. During the assembly of the mesenchyme cells into pretubular aggregates, syndecan was detected in these aggregates and, to a lesser degree, in the morphologically undifferentiated mesenchyme. Thereafter syndecan was found only in the differentiating epithelium, from which it was gradually lost during maturation of the nephron. It was last detected in the periphery of the kidney, where tubulogenesis still continued. In transfilter cultures we showed that syndecan appeared in the nephric mesenchyme during the period when the mesenchyme becomes programmed to transform into epithelial structures. By using interspecies recombinations and a species-specific antibody we excluded the possibility that syndecan in the mesenchyme would originate from the inductor. We conclude that syndecan expression is regulated by epithelial-mesenchymal interactions. The findings that syndecan appeared as an early response to induction and that its distribution showed both spatial and temporal correlation with kidney morphogenesis suggest an important role for this molecule in development.

Animals↗
PubMed1989

Syndecan and tenascin expression is induced by epithelial-mesenchymal interactions in embryonic tooth mesenchyme.

Morphogenesis of embryonic organs is regulated by epithelial-mesenchymal interactions associating with changes in the extracellular matrix (ECM). The response of the cells to the changes in the ECM must involve integral cell surface molecules that recognize their matrix ligand and initiate transmission of signal intracellularly. We have studied the expression of the cell surface proteoglycan, syndecan, which is a matrix receptor for epithelial cells (Saunders, S., M. Jalkanen, S. O'Farrell, and M. Bernfield. J. Cell Biol. In press.), and the matrix glycoprotein, tenascin, which has been proposed to be involved in epithelial-mesenchymal interactions (Chiquet-Ehrismann, R., E. J. Mackie, C. A. Pearson, and T. Sakakura. 1986. Cell. 47:131-139) in experimental tissue recombinations of dental epithelium and mesenchyme. Our earlier studies have shown that in mouse embryos both syndecan and tenascin are intensely expressed in the condensing dental mesenchyme surrounding the epithelial bud (Thesleff, I., M. Jalkanen, S. Vainio, and M. Bernfield. 1988. Dev. Biol. 129:565-572; Thesleff, I., E. Mackie, S. Vainio, and R. Chiquet-Ehrismann. 1987. Development. 101:289-296). Analysis of rat-mouse tissue recombinants by a monoclonal antibody against the murine syndecan showed that the presumptive dental epithelium induces the expression of syndecan in the underlying mesenchyme. The expression of tenascin was induced in the dental mesenchyme in the same area as syndecan. The syndecan and tenascin positive areas increased with time of epithelial-mesenchymal contact. Other ECM molecules, laminin, type III collagen, and fibronectin, did not show a staining pattern similar to that of syndecan and tenascin. Oral epithelium from older embryos had lost its ability to induce syndecan expression but the presumptive dental epithelium induced syndecan expression even in oral mesenchyme of older embryos. Our results indicate that the expression of syndecan and tenascin in the tooth mesenchyme is regulated by epithelial-mesenchymal interactions. Because of their early appearance, syndecan and tenascin may be used to study the molecular regulation of this interaction. The similar distribution patterns of syndecan and tenascin in vivo and in vitro and their early appearance as a result of epithelial-mesenchymal interaction suggest that these molecules may be involved in the condensation and differentiation of dental mesenchymal cells.

Animals↗