Genes affecting tooth morphogenesis

Abstract

The development of dentition is a fascinating process that encompasses a complex series of epithelial-mesenchymal interactions involving growth factors, transcription factors, signal receptors and other soluble morphogens. It is not surprising that such a complex process is prone to disturbances and may result in tooth agenesis. Initial discoveries indicating that the homeo-domain protein MSX1 and the paired-domain transcription factor PAX9 are causative genes in tooth morphogenesis were made in mice. Both genes are co-expressed in dental mesenchyme and either one, when homozygously deleted, results in an arrest at an early developmental stage. Previous studies have shown a down regulation of Bmp4 gene expression in Pax9 and Msx1 single mutant mice. Therefore, we chose to explore the molecular relationship between Pax9, Msx1 and Bmp4. In humans, unlike in mice, a heterozygous mutation in either PAX9 or MSX1 suffices to cause tooth agenesis of a predominantly molar or more premolar pattern, respectively. Our laboratory and others have identified several PAX9 and MSX1 mutations in families with non-syndromic forms of autosomal dominant posterior tooth agenesis. We have also identified families with tooth agenesis in whom PAX9 and MSX1 mutations have been excluded opening up the possibilities for the discovery of other genes that contribute to human tooth agenesis.

Tooth Agenesis: from Molecular Genetics to Molecular Dentistry

“…Differences in tooth size and the whole distribution of the dentition may also be observed, especially in more severe cases of oligodontia. The molecular basis of the defect is not completely understood, despite identification of several mutations in MSX1 and PAX9 genes that seem to be crucial for tooth agenesis (recently reviewed in Kapadia et al, 2007), and mutations in the AXIN2 gene that cause oligodontia together with a predisposition to colorectal cancer. Msx1 and Pax9 are transcription factors necessary for normal development.…”

Internal Root Resorption: A Review

“…Odontoblasts are postmitotic cells that are incapable of cell division following their terminal differentiation. Despite the advances in our understanding of the molecular signaling that determines cell fate during tooth morphogenesis and regeneration (81,82), the precise cross-talk mechanisms that determine the commitment of mesenchymal progenitor cells to a definitive odontoblast lineage (as opposed to the osteoblast lineage) remain ambiguous at large (83,84). In the absence of highly specific epigenetically derived signals required for lineage diversification and differentiation of ''true'' odontoblasts in an adult tooth, multipotent stem cells engaged in the process of reparative dentin formation retain the osteoblastic phenotype and secrete a matrix that more resembles bone than dentin.…”

Esthetic management of a rare non-syndromic hypodontia case

“…On the basis of the knowledge of genes and transcription factors that are involved in tooth development, it is assumed that different phenotypic forms are caused by different genes involving different interacting molecular pathways. The genes involved in human non-syndromic hypodontia include not only those encoding a signaling molecule (TGFA) and transcription factors (MSX1 & PAX9) but also genes coding for a protein involved in canonical Wnt signaling (AX1N2) and a transmembrane receptor of fibroblast growth factor (FGFR1) [13][14][15][16][17]. The consequences of missing teeth are numerous and depend on the number and type of teeth that are missing.…”