Pitx2 regulates lung asymmetry, cardiac positioning and pituitary and tooth morphogenesis

Chijen R. Lin, Chrissa Kioussi, Shawn O'Connell, Paola Briata, Daniel Szeto, Forrest Liu, Juan Carlos Izpisúa-Belmonte () and Michael G. Rosenfeld ()
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Chijen R. Lin: Howard Hughes Medical Institute, University of California
Chrissa Kioussi: Howard Hughes Medical Institute, University of California
Shawn O'Connell: Howard Hughes Medical Institute, University of California
Paola Briata: Howard Hughes Medical Institute, University of California
Daniel Szeto: Howard Hughes Medical Institute, University of California
Forrest Liu: Howard Hughes Medical Institute, University of California
Juan Carlos Izpisúa-Belmonte: The Salk Institute for Biological Studies
Michael G. Rosenfeld: Howard Hughes Medical Institute, University of California

Nature, 1999, vol. 401, issue 6750, 279-282

Abstract: Abstract Pitx1 (refs 1,2,3) and Pitx2 (refs 4, 5) are highly homologous, bicoid-related transcription factors. Pitx2 was initially identified as the gene responsible for the human Rieger syndrome4, an autosomal dominant condition that causes developmental abnormalities. Pitx2 is asymmetrically expressed in the left lateral-plate mesoderm5,6,7,8,9,10,11, and mutant mice with laterality defects show altered patterns of Pitx2 expression that correlate with changes in the visceral symmetry (situs). Ectopic expression of Pitx2 in the right lateral-plate mesoderm alters looping of the heart and gut and reverses body rotation in chick and Xenopus embryos6,7,8,9,10,11. Here we describe the phenotype of Pitx2 gene-deleted mice, characterized by defective body-wall closure, right pulmonary isomerism, altered cardiac position, arrest in turning and, subsequently, a block in the determination and proliferation events of anterior pituitary gland and tooth organogenesis. Thus, Pitx2 is a transcription factor that encodes ‘leftness’ of the lung.

Date: 1999
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DOI: 10.1038/45803

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