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: 6.27). 03/1993; 117(2):461-70.
Source: PubMed

ABSTRACT 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, Aug 19, 2015
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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 · 3.50 Impact Factor
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    • "It has been well documented that epithelial– mesenchymal interactions play an important role during organogenesis in vertebrate organs such as the kidney (Bard 1996; Peters & Balling 1999; Bard et al. 2001; Yu et al. 2004), lung (Minoo & King 1994; Prodhan & Kinane 2002; Sakiyama et al. 2003), tooth (Jowett et al. 1993; Peters & Balling 1999) and limbs (Liu et al. 2003). Vertebrate digestive organs are composed of an epithelial lining that originates from endoderm and a surrounding mesenchyme that is derived from splanchnic mesoderm (Romanoff 1960). "
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    Development Growth and Regeneration 09/2005; 47(6):375-82. DOI:10.1111/j.1440-169X.2005.00816.x · 2.18 Impact Factor
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    • "The preparation of the following RNA probes has previously been described: Msx2 (Jowett et al. 1993), pro ␣ 1(I) collagen and pro ␣ 1(II) collagen (Metsäranta et al. 1991), and Bsp (Rice et al. 2000). The 500-bp Sox9 plasmid and the 600-bp 5 Ј PstI-HindIII fragment of murine "
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    ABSTRACT: Facial and calvarial bones form intramembranously without a cartilagenous model; however, cultured chick calvarial mesenchyme cells may differentiate into both osteoblasts and chondroblasts and, in rodents, small cartilages occasionally form at the sutures in vivo. Therefore, we wanted to investigate what factors regulate normal differentiation of calvarial mesenchymal cells directly into osteoblasts. In embryonic mouse heads and in cultured tissue explants, we analyzed the expression of selected transcription factors and extracellular matrix molecules associated with bone and cartilage development. Cartilage markers Sox9 and type II collagen were expressed in all craniofacial cartilages. In addition, Msx2 and type I collagen were expressed in sense capsule cartilages. We also observed that the undifferentiated calvarial mesenchyme and the osteogenic fronts in the jaw expressed Col2A1. Moreover, we found that cultured mouse calvarial mesenchyme could develop into cartilage. Of the 49 explants that contained mesenchyme, intramembranous ossification occurred in 35%. Only cartilage formed in 4%, and both cartilage and bone formed in 4%. Our study confirms that calvarial mesenchyme, which normally gives rise to intramembranous bone, also has chondrogenic potential.
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