Epithelial–mesenchyme 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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Available from: Adrian K Jowett, Oct 04, 2015
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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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    ABSTRACT: Tooth agenesis is one of the most common congenital malformations in humans. Hypodontia can either occur as an isolated condition (non-syndromic hypodontia) or can be associated with a syndrome (syndromic hypodontia), highlighting the heterogeneity of the condition. Though much progress has been made to identify the developmental basis of tooth formation, knowledge of the etiological basis of inherited tooth loss is still lacking. To date, the mutation spectra of non-syndromic form of familial and sporadic tooth agenesis in humans have revealed defects in various such genes that encode transcription factors, MSX1 and PAX9 or genes that code for a protein involved in canonical Wnt signaling (AXIN2), and a transmembrane receptor of fibroblast growth factors (FGFR1). The aim of this paper is to review the current literature on the molecular mechanisms responsible for selective hypodontia in humans and to present a detailed overview of causative genes and syndromes associated with hypodontia. Key words:Tooth agenesis, hypodontia, growth factors, mutations.
    Medicina oral, patologia oral y cirugia bucal 10/2013; 19(2). DOI:10.4317/medoral.19158 · 1.17 Impact Factor
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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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    ABSTRACT: The interruption of odontogenesis by any etiological factor may result in dental anomalies. Apart from the environmental factors, the impact of genetics in dental anomalies was found to be a factor in different levels. Many authors had questioned a common genetic defect resulting in different phenotypic conditions such as absent, malformed, malposed or ectopic teeth. Because the multidisciplinary treatment of these dental anomalies such as hypodontia, impaction etc., involves orthodontic intervention, orthodontists must be aware of the etiology and possible correlative conditions with dental anomalies.
    European journal of dentistry 09/2013; 7(Suppl 1):S143-7. DOI:10.4103/1305-7456.119092
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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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    ABSTRACT: MSX2, a member of the homeobox genes family, is demonstrated to be the downstream target for ras signaling pathway and is expressed in a variety of carcinoma cells, suggesting its relevance to the development of ductal pancreatic tumors since pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary-mucinous neoplasia (IPMN) harbor frequent K-ras gene mutations. Recent studies revealed the roles of MSX2 in the development of carcinoma of various origins including pancreas. Among gastrointestinal tumors, PDAC is one of the most malignant. PDAC progresses rapidly to develop metastatic lesions, frequently by the time of diagnosis, and these tumors are usually resistant to conventional chemotherapy and radiation therapy. The molecular mechanisms regulating the aggressive behavior of PDAC still remain to be clarified. On the other hand, IPMN of the pancreas is distinct from PDAC because of its intraductal growth in the main pancreatic duct or secondary branches with rare invasion and metastasis to distant organs. However, recent evidence indicated that once IPMN showed stromal invasion, it progresses like PDAC. Therefore, it is important to determin how IPMN progresses to malignant phenotype. In this review, we focus on the involvement of MSX2 in the enhancement of malignant behavior in PDAC and IPMN, and further highlight the clinical approach to differentiate PDAC from chronic pancreatitis by evaluating MSX2 expression level.
    Frontiers in Physiology 11/2012; 3:430. DOI:10.3389/fphys.2012.00430 · 3.53 Impact Factor
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