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The Role of PITX2 in Tooth Development

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The Molecular Mechanisms of Axenfeld-Rieger Syndrome

Part of the book series: Medical Intelligence Unit ((MIUN))

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Abstract

The transcriptional mechanisms underlying tooth development are only beginning to be understood. Axenfeld-Rieger syndrome (ARS) patients provided the first link of PITX2 to tooth development. ARS patients present clinically with dental hypoplasia, which includes microdontia, hypodontia and misshapen teeth. Pitx2 is the earliest known transcription factor that is selectively expressed in the oral ectoderm. Since Pitx2, Msx2, Left and Dlx2 are expressed in the dental epithelium we are examining the transcriptional activity of PITX2 in concert with these factors. We demonstrate that Msx2 binds to a variety of DNA elements and may play a more central role in regulating genes in tissues expressing this transcriptional repressor. We have identified the Dlx2 promoter as a target of PITX2 during tooth development. Msx2 represses the Dlx2 promoter and coexpression of both PITX2 and Msx2 resulted in transcriptional antagonism of the Dlx2 promoter. Furthermore, a PITX2A mutation associated with ARS (PITX2A T68P) is unable to transactivate the Dlx2 promoter. ARS patients with this point mutation present clinically with missing teeth. In contrast, a patient that presents clinically with only iris hypoplasia and normal tooth development has a PITX2A mutation (PITX2A R84W) that transactivates the Dlx2 promoter. These data suggest a molecular mechanism for the dental anomalies associated with Axenfeld-Rieger syndrome. We will review the role of PITX2 in tooth development and speculate on potential downstream targets of PITX2.

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Authors and Affiliations

  1. Health Science Center, Institute of Biosciences and Technology, Center for Environmental and Genetic Medicine, The Texas A&M University System, Houston, Texas, USA

    Brad A. Amendt Ph.D.

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  1. Brad A. Amendt Ph.D.
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Amendt, B.A. (2005). The Role of PITX2 in Tooth Development. In: The Molecular Mechanisms of Axenfeld-Rieger Syndrome. Medical Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-28672-1_8

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