Ryan A K, Blumberg B, Rodriguez-Esteban C, Yonei-Tamura S, Tamura K, Tsukui T, de la Peña J, Sabbagh W, Greenwald J, Choe S, Norris D P, Robertson E J, Evans R M, Rosenfeld M G, Izpisúa Belmonte J C
Howard Hughes Medical Institute, University of California, San Diego, La Jolla 92093-0648, USA.
Nature. 1998 Aug 6;394(6693):545-51. doi: 10.1038/29004.
The handedness of visceral organs is conserved among vertebrates and is regulated by asymmetric signals relayed by molecules such as Shh, Nodal and activin. The gene Pitx2 is expressed in the left lateral plate mesoderm and, subsequently, in the left heart and gut of mouse, chick and Xenopus embryos. Misexpression of Shh and Nodal induces Pitx2 expression, whereas inhibition of activin signalling blocks it. Misexpression of Pitx2 alters the relative position of organs and the direction of body rotation in chick and Xenopus embryos. Changes in Pitx2 expression are evident in mouse mutants with laterality defects. Thus, Pitx2 seems to serve as a critical downstream transcription target that mediates left-right asymmetry in vertebrates.
内脏器官的左右不对称性在脊椎动物中是保守的,并且由诸如Shh、Nodal和激活素等分子传递的不对称信号所调控。基因Pitx2在小鼠、鸡和非洲爪蟾胚胎的左侧侧板中胚层中表达,随后在左侧心脏和肠道中表达。Shh和Nodal的错误表达会诱导Pitx2的表达,而激活素信号传导的抑制则会阻断它。Pitx2的错误表达会改变鸡和非洲爪蟾胚胎中器官的相对位置和身体旋转方向。在具有左右不对称缺陷的小鼠突变体中,Pitx2表达的变化很明显。因此,Pitx2似乎作为一个关键的下游转录靶点,介导脊椎动物的左右不对称性。