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  • Title: Genes affecting tooth morphogenesis.
    Author: Kapadia H, Mues G, D'Souza R.
    Journal: Orthod Craniofac Res; 2007 Nov; 10(4):237-44. PubMed ID: 17973693.
    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.
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