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

Development ◽  
1993 ◽  
Vol 117 (2) ◽  
pp. 461-470 ◽  
Author(s):  
A.K. Jowett ◽  
S. Vainio ◽  
M.W. Ferguson ◽  
P.T. Sharpe ◽  
I. Thesleff
Keyword(s):  
Gene Expression ◽  
Tooth Development ◽  
Homeobox Gene ◽  
Oral Epithelium ◽  
Tooth Formation ◽  
Dental Papilla ◽  
Tissue Interactions ◽  
Dental Epithelium

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.

Tissue interactions in embryonic mouse tooth germs

Development ◽  
1970 ◽  
Vol 24 (1) ◽  
pp. 159-171
Author(s):  
Edward J. Kollar ◽  
Grace R. Baird
Keyword(s):  
Enamel Organ ◽  
Oral Epithelium ◽  
Embryonic Mouse ◽  
Tooth Shape ◽  
Structural Specificity ◽  
Dental Papilla ◽  
Tissue Interactions ◽  
Dental Epithelium ◽  
Tooth Germs

The ability of fragments of incisor enamel organ and lip-furrow epithelium from 15- and 16-day old embryonic mice to regulate into harmonious tooth constructions is described. The cervical loop and upper half portions of the incisor enamel organ were confronted with incisor or molar dental papillae. Similar combinations were made from lip-furrow epithelium and incisor or molar papillae. The cultures were grown in the anterior chambers of homologous host eyes. The epithelial fragments from the incisor enamel organ when associated with the dental papillae reconstruct teeth typical in all respects; enamel and dentin matrices are deposited. Lip-furrow epithelium arises from the oral epithelium and is temporally and spatially related to the incisor dental epithelium proper. This ectopic epithelium was confronted by incisor and molar papillae. Harmonious teeth developed in these explants. It is concluded that the ability of the dental papillae to elicit new cytodifferentiative and biochemical syntheses from the lip-furrow epithelium indicates that the dental papillae act inductively during tooth ontogeny. The shape of the teeth reconstructed from enamel organ fragments and lip-furrow epithelium were incisiform or molariform in response to the incisor or molar dental papillae. These data confirm the conclusion that the structural specificity for tooth shape resides in the dental papilla.

scholarly journals Interaction of Vav with ENX-1, a putative transcriptional regulator of homeobox gene expression.

1996 ◽  
Vol 16 (6) ◽  
pp. 3066-3073 ◽  
Author(s):  
O Hobert ◽  
B Jallal ◽  
A Ullrich
Keyword(s):  
Gene Expression ◽  
Critical Role ◽  
Homeobox Gene ◽  
Transcriptional Regulators ◽  
Polycomb Group ◽  
Yeast Two Hybrid ◽  
Yeast Two Hybrid System ◽  
Two Hybrid

The proto-oncogene product Vav plays a critical role in hematopoietic signal transduction. By using the yeast two-hybrid system, we identified a novel human protein, ENX-1, which interacts specifically with Vav both in vitro and in vivo. ENX-1 represents the human homolog of the Drosophila Enhancer of zeste gene, a member of the Polycomb group of genes, which are transcriptional regulators of homeobox gene expression. Interaction with ENX-1 suggests that Vav functions as an upstream element in the transcriptional regulation of homeobox genes, known to be important effectors in the hematopoietic system.

The Genetic Control of Early Tooth Development

1997 ◽  
Vol 8 (1) ◽  
pp. 4-39 ◽  
Author(s):  
R. Maas ◽  
M. Bei
Keyword(s):  
Tooth Development ◽  
Homeobox Gene ◽  
Experimental System ◽  
Tooth Germ ◽  
Tooth Formation ◽  
Tissue Interactions ◽  
Bmp4 Expression ◽  
Msx Genes ◽  
Deficient Mice

Most vertebrate organs begin their initial formation by a common, developmentally conserved pattern of inductive tissue interactions between two tissues. The developing tooth germ is a prototype for such inductive tissue interactions and provides a powerful experimental system for elucidation of the genetic pathways involved in organogenesis. Members of the Msx homeobox gene family are expressed at sites of epithelial-mesenchymal interaction during embryogenesis, including the tooth. The important role that Msx genes play in tooth development is exemplified by mice lacking Msx gene function. Msxldeficient mice exhibit an arrest in tooth development at the bud stage, while Msx2-deficient mice exhibit late defects in tooth development. The co-expression of Msx, Bmp, L ef1, and Activin βA genes and the coincidence of tooth phenotypes in the various knockout mice suggest that these genes reside within a common genetic pathway. Results summarized here indicate that Msx1 is required for the transmission of Bmp4 expression from dental epithelium to mesenchyme and also for L ef1 expression. In addition, we consider the role of other signaling molecules in the epithelial-mesenchymal interactions leading to tooth formation, the role that transcription factors such as Msx play in the propagation of inductive signals, and the role of extracellular matrix. Last, as a unifying mechanism to explain the disparate tooth phenotypes in Msxl- and Msx2-deficient mice, we propose that later steps in tooth morphogenesis molecularly resemble those in early tooth development.

scholarly journals HDAC6 Regulates the Fusion of Autophagosome and Lysosome to Involve in Odontoblast Differentiation

2020 ◽  
Vol 8 ◽  
Author(s):  
Yunyan Zhan ◽  
Haisheng Wang ◽  
Lu Zhang ◽  
Fei Pei ◽  
Zhi Chen
Keyword(s):  
Tooth Development ◽  
Expression Patterns ◽  
Autophagic Flux ◽  
Differentiation Capacity ◽  
Odontoblast Differentiation ◽  
Dental Papilla ◽  
Odontoblastic Differentiation ◽  
Dental Papilla Cells

Odontoblast differentiation is an important process during tooth development in which pre-odontoblasts undergo elongation, polarization, and finally become mature secretory odontoblasts. Many factors have been found to regulate the process, and our previous studies demonstrated that autophagy plays an important role in tooth development and promotes odontoblastic differentiation in an inflammatory environment. However, it remains unclear how autophagy is modulated during odontoblast differentiation. In this study, we found that HDAC6 was involved in odontoblast differentiation. The odontoblastic differentiation capacity of human dental papilla cells was impaired upon HDAC6 inhibition. Moreover, we found that HDAC6 and autophagy exhibited similar expression patterns during odontoblast differentiation both in vivo and in vitro; the expression of HDAC6 and the autophagy related proteins ATG5 and LC3 increased as differentiation progressed. Upon knockdown of HDAC6, LC3 puncta were increased in cytoplasm and the autophagy substrate P62 was also increased, suggesting that autophagic flux was affected in human dental papilla cells. Next, we determined the mechanism during odontoblastic differentiation and found that the HDAC6 substrate acetylated-Tubulin was up-regulated when HDAC6 was knocked down, and LAMP2, LC3, and P62 protein levels were increased; however, the levels of ATG5 and Beclin1 showed no obvious change. Autophagosomes accumulated while the number of autolysosomes was decreased as determined by mRFP-GFP-LC3 plasmid labeling. This suggested that the fusion between autophagosomes and lysosomes was blocked, thus affecting the autophagic process during odontoblast differentiation. In conclusion, HDAC6 regulates the fusion of autophagosomes and lysosomes during odontoblast differentiation. When HDAC6 is inhibited, autophagosomes can't fuse with lysosomes, autophagy activity is decreased, and it leads to down-regulation of odontoblastic differentiation capacity. This provides a new perspective on the role of autophagy in odontoblast differentiation.

scholarly journals Insight into the maintenance of odontogenic potential in mouse dental mesenchymal cells based on transcriptomic analysis

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1684 ◽  
Author(s):  
Yunfei Zheng ◽  
Lingfei Jia ◽  
Pengfei Liu ◽  
Dandan Yang ◽  
Waner Hu ◽  
...  
Keyword(s):  
Tooth Development ◽  
Differential Expression Analysis ◽  
Mesenchymal Cells ◽  
Genes Encoding ◽  
Dental Epithelium ◽  
Wnt Pathways ◽  
Tooth Germs ◽  
Insight Into

Background.Mouse dental mesenchymal cells (mDMCs) from tooth germs of cap or later stages are frequently used in the context of developmental biology or whole-tooth regeneration due to their odontogenic potential.In vitro-expanded mDMCs serve as an alternative cell source considering the difficulty in obtaining primary mDMCs; however, cultured mDMCs fail to support tooth development as a result of functional failures of specific genes or pathways. The goal of this study was to identify the genes that maintain the odontogenic potential of mDMCs in culture.Methods.We examined the odontogenic potential of freshly isolated versus cultured mDMCs from the lower first molars of embryonic day 14.5 mice. The transcriptome of mDMCs was detected using RNA sequencing and the data were validated by qRT-PCR. Differential expression analysis and pathway analysis were conducted to identify the genes that contribute to the loss of odontogenic potential.Results.Cultured mDMCs failed to develop into well-structured tooth when they were recombined with dental epithelium. Compared with freshly isolated mDMCs, we found that 1,004 genes were upregulated and 948 were downregulated in cultured mDMCs. The differentially expressed genes were clustered in the biological processes and signaling pathways associated with tooth development. Followingin vitroculture, genes encoding a wide array of components of MAPK, TGF-β/BMP, and Wnt pathways were significantly downregulated. Moreover, the activities ofBdnf,Vegfα,Bmp2, andBmp7were significantly inhibited in cultured mDMCs. Supplementation of VEGFα, BMP2, and BMP7 restored the expression of a subset of downregulated genes and induced mDMCs to form dentin-like structuresin vivo.Conclusions.Vegfα,Bmp2, andBmp7play a role in the maintenance of odontogenic potential in mDMCs.

BMP4 rescues a non-cell-autonomous function of Msx1 in tooth development

Development ◽  
2000 ◽  
Vol 127 (21) ◽  
pp. 4711-4718 ◽  
Author(s):  
M. Bei ◽  
K. Kratochwil ◽  
R.L. Maas
Keyword(s):  
Dental Pulp ◽  
Tooth Development ◽  
Survival Function ◽  
Tooth Germ ◽  
Tooth Formation ◽  
Kidney Capsule ◽  
Dependent Signal ◽  
Dental Epithelium ◽  
Tooth Germs

The development of many organs depends on sequential epithelial-mesenchymal interactions, and the developing tooth germ provides a powerful model for elucidating the nature of these inductive tissue interactions. In Msx1-deficient mice, tooth development arrests at the bud stage when Msx1 is required for the expression of Bmp4 and Fgf3 in the dental mesenchyme (Bei, M. and Maas, R. (1998) Development 125, 4325–4333). To define the tissue requirements for Msx1 function, we performed tissue recombinations between wild-type and Msx1 mutant dental epithelium and mesenchyme. We show that through the E14.5 cap stage of tooth development, Msx1 is required in the dental mesenchyme for tooth formation. After the cap stage, however, tooth development becomes Msx1 independent, although our experiments identify a further late function of Msx1 in odontoblast and dental pulp survival. These results suggest that prior to the cap stage, the dental epithelium receives an Msx1-dependent signal from the dental mesenchyme that is necessary for tooth formation. To further test this hypothesis, Msx1 mutant tooth germs were first cultured with either BMP4 or with various FGFs for two days in vitro and then grown under the kidney capsule of syngeneic mice to permit completion of organogenesis and terminal differentiation. Previously, using an in vitro culture system, we showed that BMP4 stimulated the growth of Msx1 mutant dental epithelium (Chen, Y., Bei, M. Woo, I., Satokata, I. and Maas, R. (1996). Development 122, 3035–3044). Using the more powerful kidney capsule grafting procedure, we now show that when added to explanted Msx1-deficient tooth germs prior to grafting, BMP4 rescues Msx1 mutant tooth germs all the way to definitive stages of enamel and dentin formation. Collectively, these results establish a transient functional requirement for Msx1 in the dental mesenchyme that is almost fully supplied by BMP4 alone, and not by FGFs. In addition, they formally prove the postulated downstream relationship of BMP4 with respect to Msx1, establish the non-cell-autonomous nature of Msx1 during odontogenesis, and disclose an additional late survival function for Msx1 in odontoblasts and dental pulp.

The homeobox gene Hox 7.1 has specific regional and temporal expression patterns during early murine craniofacial embryogenesis, especially tooth development in vivo and in vitro

Development ◽  
1991 ◽  
Vol 111 (2) ◽  
pp. 269-285 ◽  
Author(s):  
A. Mackenzie ◽  
G.L. Leeming ◽  
A.K. Jowett ◽  
M.W. Ferguson ◽  
P.T. Sharpe
Keyword(s):  
Neural Crest ◽  
Tooth Development ◽  
Expression Patterns ◽  
Homeobox Gene ◽  
Branchial Arch ◽  
Developing Brain ◽  
Stage Of Development ◽  
Tooth Germs

Hox 7.1 is a murine homeobox-containing gene expressed in a range of neural-crest-derived tissues and areas of putative epithelial-mesenchymal interactions during embryogenesis. We have examined the expression of Hox 7.1 during craniofacial development in the mouse embryo between days 8 and 16 of development. Whereas facial expression at day 10 of gestation is broadly localised in the neural-crest-derived mesenchyme of the medial nasal, lateral nasal, maxillary and mandibular processes, by day 12 expression is restricted to the mesenchyme immediately surrounding the developing tooth germs in the maxillary and mandibular processes. Hox 7.1 expression in the mesenchyme of the dental papilla and follicle is maximal at the cap stage of development and progressively declines in the bell stage prior to differentiation of odontoblasts and ameloblasts. Hox 7.1 expression in tooth germs is independent of overall embryonic stage of development but is dependent on stage of development of the individual tooth. Similar patterns of transient Hox 7.1 expression can also be detected in tooth germs in vitro in organ cultures of day 11 first branchial arch explants cultured for up to 7 days. Hox 7.1 is also expressed early in development (days 10/11) in the epithelium of the developing anterior pituitary (Rathke's pouch), the connective tissue capsule and meninges of the developing brain, and specific regions of neuroepithelium in the developing brain.

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

1989 ◽  
Vol 108 (5) ◽  
pp. 1945-1953 ◽  
Author(s):  
S Vainio ◽  
M Jalkanen ◽  
I Thesleff
Keyword(s):  
Cell Surface ◽  
Distribution Patterns ◽  
Mouse Tissue ◽  
Oral Epithelium ◽  
Type Iii Collagen ◽  
Similar Distribution ◽  
Early Appearance ◽  
Dental Epithelium

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.

scholarly journals Identification and characterization of enamel proteinases isolated from developing enamel. Amelogeninolytic serine proteinases are associated with enamel maturation in pig

1988 ◽  
Vol 256 (3) ◽  
pp. 965-972 ◽  
Author(s):  
C M Overall ◽  
H Limeback
Keyword(s):  
Developmental Stages ◽  
Tooth Development ◽  
Serine Proteinases ◽  
Protein Matrix ◽  
Enamel Matrix Proteins ◽  
Tooth Formation ◽  
Enamel Protein ◽  
Enamel Proteins

During tooth formation nearly all of the protein matrix of enamel is removed before final mineralization. To study this process, enamel proteins and proteinases were extracted from pig enamel at different stages of tooth development. In the enamel maturation zones, the major enamel matrix proteins, the amelogenins, were rapidly processed and removed. Possibly associated with this process in vivo are two groups of proteinases which were identified in the enamel extracts by enzymography using amelogenin-substrate and gelatin-substrate polyacrylamide gels and by the degradation in vitro of guanidinium chloride-extracted amelogenins. One group of proteinases with gelatinolytic activity consisted of several neutral metalloendoproteinases having Mr values from 62,000 to 130,000. These proteinases were inactive against amelogenins, casein and albumin, and were present in approximately equal proportions in enamel at all developmental stages. In the other group, two serine proteinases, with apparent non-reduced Mr of 31,000 and 36,000 exhibited amelogeninolytic activity. The substrate preference of the enamel serine proteinases was indicated by their limited degradation of casein and their inability to degrade gelatin and albumin. Contrasting with the distribution of the metalloendoproteinase enzymes, the serine proteinases were found only in the enamel scrapings taken from late-maturing enamel. The amelogenin degradation patterns in vivo, observed in the enamel scrapings, were similar to those produced in assays in vitro using partially purified fractions of enamel proteinases and amelogenin substrate. Together, these data strongly indicate an important role for the serine proteinases, and possibly the gelatinolytic proteinases, in the organized processing of the enamel protein matrix during enamel formation.

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