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Molecular and Cellular Biology, August 2007, p. 5765-5775, Vol. 27, No. 16
0270-7306/07/$08.00+0     doi:10.1128/MCB.01848-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Nuclear Factor 1 and T-Cell Factor/LEF Recognition Elements Regulate Pitx2 Transcription in Pituitary Development{triangledown}

Di Ai, Jun Wang, Melanie Amen, Mei-Fang Lu, Brad A. Amendt, and James F. Martin*

Institute of Biosciences and Technology, Texas A&M System Health Science Center, 2121 Holcombe Blvd, Houston, Texas 77030

Received 29 September 2006/ Returned for modification 17 January 2007/ Accepted 21 May 2007

Pitx2, a paired-related homeobox gene that is mutated in Rieger syndrome I, is the earliest known marker of oral ectoderm. Pitx2 was previously shown to be required for tooth, palate, and pituitary development in mice; however, the mechanisms regulating Pitx2 transcription in the oral ectoderm are poorly understood. Here we used an in vivo transgenic approach to investigate the mechanisms regulating Pitx2 transcription. We identified a 7-kb fragment that directs LacZ expression in oral ectoderm and in many of its derivatives. Deletion analysis of transgenic embryos reduced this fragment to a 520-bp region that directed LacZ activity to Rathke's pouch. A comparison of the mouse and human sequences revealed a conserved nuclear factor 1 (NF-1) recognition element near a consensus T-cell factor (TCF)/LEF binding site. The mutation of either site individually abolished LacZ activity in transgenic embryos, identifying Pitx2 as a direct target of Wnt signaling in pituitary development. These findings uncover a requirement for NF-1 and TCF factors in Pitx2 transcriptional regulation in the pituitary and provide insight into the mechanisms controlling region-specific transcription in the oral ectoderm and its derivatives.

* Corresponding author. Mailing address: Institute of Biosciences and Technology, Texas A&M System Health Science Center, 2121 Holcombe Blvd., Houston, TX 77030. Phone: (713) 677-7558. Fax: (713) 677-7512. E-mail: jmartin{at}ibt.tamhsc.edu

{triangledown} Published ahead of print on 11 June 2007.

Molecular and Cellular Biology, August 2007, p. 5765-5775, Vol. 27, No. 16
0270-7306/07/$08.00+0     doi:10.1128/MCB.01848-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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