QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online November 17, 2003
doi: 10.1242/10.1242/dev.00849

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, W. Articles by Martin, J. F. Search for Related Content PubMed PubMed Citation Articles by Liu, W. Articles by Martin, J. F.

Genetic dissection of Pitx2 in craniofacial development uncovers new functions in branchial arch morphogenesis, late aspects of tooth morphogenesis and cell migration

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

^* Author for correspondence (e-mail: jmartin{at}ibt.tamushsc.edu)

Accepted 1 September 2003

Pitx2, a paired-related homeobox gene that encodes multiple isoforms, is the gene mutated in the haploinsufficient Rieger Syndrome type 1 that includes dental, ocular and abdominal wall anomalies as cardinal features. Previous analysis of the craniofacial phenotype of Pitx2-null mice revealed that Pitx2 was both a positive regulator of Fgf8 and a repressor of Bmp4-signaling, suggesting that Pitx2 may function as a coordinator of craniofacial signaling pathways. We show that Pitx2 isoforms have interchangeable functions in branchial arches and that Pitx2 target pathways respond to small changes in total Pitx2 dose. Analysis of Pitx2 allelic combinations that encode varying levels of Pitx2 showed that repression of Bmp signaling requires high Pitx2 while maintenance of Fgf8 signaling requires only low Pitx2. Fate-mapping studies with a Pitx2 cre recombinase knock in allele revealed that Pitx2 daughter cells are migratory and move aberrantly in the craniofacial region of Pitx2 mutant embryos. Our data reveal that Pitx2 function depends on total Pitx2 dose and rule out the possibility that the differential sensitivity of target pathways was a consequence of isoform target specificity. Moreover, our results uncover a new function of Pitx2 in regulation of cell motility in craniofacial development.

Key words: Homeobox, Craniofacial morphogenesis, Haploinsufficiency

This article has been cited by other articles:

				Inaugural Article: The direction of gut looping is established by changes in the extracellular matrix and in cell:cell adhesion PNAS, June 24, 2008; 105(25): 8499 - 8506.

				M. Amen, X. Liu, U. Vadlamudi, G. Elizondo, E. Diamond, J. F. Engelhardt, and B. A. Amendt PITX2 and {beta}-Catenin Interactions Regulate Lef-1 Isoform Expression Mol. Cell. Biol., November 1, 2007; 27(21): 7560 - 7573. [Abstract] [Full Text] [PDF]

				M. T.M. Mommersteeg, N. A. Brown, O. W.J. Prall, C. de Gier-de Vries, R. P. Harvey, A. F.M. Moorman, and V. M. Christoffels Pitx2c and Nkx2-5 Are Required for the Formation and Identity of the Pulmonary Myocardium Circ. Res., October 26, 2007; 101(9): 902 - 909. [Abstract] [Full Text] [PDF]

				D. Ai, J. Wang, M. Amen, M.-F. Lu, B. A. Amendt, and J. F. Martin Nuclear Factor 1 and T-Cell Factor/LEF Recognition Elements Regulate Pitx2 Transcription in Pituitary Development Mol. Cell. Biol., August 15, 2007; 27(16): 5765 - 5775. [Abstract] [Full Text] [PDF]

				H. P. Shih, M. K. Gross, and C. Kioussi Cranial muscle defects of Pitx2 mutants result from specification defects in the first branchial arch PNAS, April 3, 2007; 104(14): 5907 - 5912. [Abstract] [Full Text] [PDF]

				F. Dong, X. Sun, W. Liu, D. Ai, E. Klysik, M.-F. Lu, J. Hadley, L. Antoni, L. Chen, A. Baldini, et al. Pitx2 promotes development of splanchnic mesoderm-derived branchiomeric muscle Development, December 15, 2006; 133(24): 4891 - 4899. [Abstract] [Full Text] [PDF]

				D. W. Stock, W. R. Jackman, and J. Trapani Developmental genetic mechanisms of evolutionary tooth loss in cypriniform fishes Development, August 15, 2006; 133(16): 3127 - 3137. [Abstract] [Full Text] [PDF]

				S. Nowotschin, J. Liao, P. J. Gage, J. A. Epstein, M. Campione, and B. E. Morrow Tbx1 affects asymmetric cardiac morphogenesis by regulating Pitx2 in the secondary heart field. Development, April 1, 2006; 133(8): 1565 - 1573. [Abstract] [Full Text] [PDF]