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

Pitx1 (refs 1-3) and Pitx2 (refs 4, 5) are highly homologous, bicoid-relate d transcription factors. Pitx2 was initially identified as the gene respons ible for the human Rieger syndrome(4), an autosomal dominant condition that causes developmental abnormalities. Pitx2 is asymmetrically expressed in t he left lateral-plate mesoderm(5-11), and mutant mice with laterality defec ts show altered patterns of Pitx2 expression that correlate with changes in the visceral symmetry (situs). Ectopic expression of Pitx2 in the right la teral-plate mesoderm alters looping of the heart and gut and reverses body rotation in chick and Xenopus embryose(6-11). Here we describe the phenotyp e 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 ant erior pituitary gland and tooth organogenesis. Thus, Pitx2 is a transcripti on factor that encodes 'leftness' of the lung.