Epithelial-mesenchymal interactions are required for MSX1 and MSX2 gene expression in the developing murine molar tooth

Department of Pedodontics and Orthodontics, University of Helsinki, Finland.
Development (Impact Factor: 6.46). 03/1993; 117(2):461-70.
Source: PubMed


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.

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    • "MSX1 contains a highly conserved homeobox sequence encoding a 60 amino acid-long DNA-binding homeodomain (21). MSX1 belongs to a family of transcription factors that are expressed in overlapping patterns at multiple sites of tissue interactions during vertebrate development (22). Till date, five point mutations have been identified within MSX1 gene mutations, with two leading to a substitution mutation within the protein and the remaining three forming a stop codon that prematurely truncates the protein. "
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    • "HOX genes are classified as muscle segment (MSX1 and MSX2), distal-less (Dlx), orthodontical, goosecoid, paired box gene 9 (Pax9) and sonic hedgehog (Shh). Msx1 and Msx2 genes are responsible for the developmental position and further development of tooth buds, respectively.[12] Dlx-1, Dlx-2[34] and Barx-1 genes[56] are involved in development of molar teeth. "
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    • "Homeobox-containing genes regulate the morphological development of a variety of organs and their expression levels vary according to the development stages of organ (Wolgemuth et al., 1989; Morgan et al., 1992). The expression of MSX2, a member of the homeobox gene (Hox gene) family, is observed in a variety of sites, including premigratory cranial neural crest, tooth, and mammary gland, etc (Takahashi and Le Douarin, 1990; Davidson et al., 1991; Monaghan et al., 1991; Jowett et al., 1993; Davidson, 1995; Friedmann and Daniel, 1996; Phippard et al., 1996). The expression pattern of this gene in the development of organs suggests its pivotal role in epithelial–mesenchymal interactions (Satoh et al., 2004). "
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