Lin C R, Kioussi C, O'Connell S, Briata P, Szeto D, Liu F, Izpisúa-Belmonte J C, Rosenfeld M G
Howard Hughes Medical Institute, Department and School of Medicine, University of California, San Diego, La Jolla 92093, USA.
Nature. 1999 Sep 16;401(6750):279-82. doi: 10.1038/45803.
Pitx1 and Pitx2 are highly homologous, bicoid-related transcription factors. Pitx2 was initially identified as the gene responsible for the human Rieger syndrome, an autosomal dominant condition that causes developmental abnormalities. Pitx2 is asymmetrically expressed in the left lateral-plate mesoderm, 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 embryos. 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.
Pitx1和Pitx2是高度同源的、与双尾相关的转录因子。Pitx2最初被鉴定为导致人类里格尔综合征的基因，这是一种常染色体显性疾病，会引起发育异常。Pitx2在左侧侧板中胚层不对称表达，具有侧位缺陷的突变小鼠显示出Pitx2表达模式的改变，这与内脏对称性（体位）的变化相关。Pitx2在右侧侧板中胚层的异位表达会改变鸡和非洲爪蟾胚胎的心脏和肠道环化，并逆转身体旋转。在此，我们描述了Pitx2基因缺失小鼠的表型，其特征为体壁闭合缺陷、右肺异构、心脏位置改变、旋转停滞，随后，垂体前叶和牙齿器官发生的决定和增殖事件受阻。因此，Pitx2是一种编码肺“左侧性”的转录因子。
