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Pitx2 controls dental stem cell proliferation and differentiation by regulating Cyclin D2 and Irx1
Abstract   Open access   Peer reviewed

Pitx2 controls dental stem cell proliferation and differentiation by regulating Cyclin D2 and Irx1

Wenjie Yu, Zhao Sun, Steven Eliason and Brad A. Amendt
The FASEB journal, Vol.31(S1)
04/2017
DOI: 10.1096/fasebj.31.1_supplement.743.10
url
https://doi.org/10.1096/fasebj.31.1_supplement.743.10View
Published (Version of record) Open Access

Abstract

Abstract only Pituitary homeobox 2 ( PITX2 ), the gene responsible for Axenfeld‐Rieger syndrome (ARS), plays a crucial role in odontogenesis. ARS individuals has dental agenesis and enamel hypoplasia. Although the function of Pitx2 in tooth development is well established, detailed cellular and molecular mechanisms of Pitx2 regulation remain unclear. Here, we conditionally ablated Pitx2 in the dental epithelium using the Krt14‐Cre ( K14 Cre Pitx2 f/f ), which resulted in arrested tooth development at the bud stage. BrdU incorporation analysis showed that cell proliferation is decreased in the K14 Cre Pitx2 f/f incisors. In addition, we found that Sox9+ cells are reduced in the dental epithelium in K14 Cre Pitx2 f/f teeth, indicating that cell differentiation is down‐regulated. We have identified Iroquois 1 (Irx1) as a new homobox transcription factor expressed in early dental development. Mechanistically, Pitx2 regulates the expression of Cyclin D2 and Irx1 to promote early tooth formation. In conclusion, we have uncovered a new Pitx2 dependent regulatory network during early tooth development. Support or Funding Information College of dentistry, the University of Iowa

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