Boettger T, Wittler L, Kessel M
Max-Planck-Institut für biophysikalische Chemie, Abteilung Molekulare Zellbiologie, D-37077 Göttingen, Germany.
Curr Biol. 1999 Mar 11;9(5):277-80. doi: 10.1016/s0960-9822(99)80119-5.
Left-right asymmetry in vertebrate embryos is first recognisable using molecular markers that encode secreted proteins or transcription factors. The asymmetry becomes morphologically obvious in the turning of the embryo and in the development of the heart, the gut and other visceral organs. In the chick embryo, a signalling pathway for the specification of the left body side was demonstrated. Here, Sonic hedgehog (Shh) protein is the first asymmetric signal identified in the node [1] [2]. Further downstream in this pathway are the left-specific genes nodal, lefty-1, lefty-2 and Pitx2 [1] [3] [4] [5]. On the right body side, a function of the activin pathway is indicated by the right-sided expression of cActRIIa [1] [6]. We detected that another key molecule in vertebrate development, fibroblast growth factor 8 (FGF8) [7] [8], is expressed asymmetrically on the right side of the posterior node. We demonstrate that transcription of FGF8 is induced by activin and the FGF8 protein inhibits the expression of nodal and Pitx2 and leads to expression of the chicken snail related gene (cSnR) [9]. Left-sided application of FGF8 randomises the direction of heart looping.
脊椎动物胚胎中的左右不对称性最初可通过编码分泌蛋白或转录因子的分子标记来识别。这种不对称性在胚胎的转动以及心脏、肠道和其他内脏器官的发育过程中在形态上变得明显。在鸡胚中，已证明存在一条用于确定左侧身体的信号通路。在此，音猬因子（Shh）蛋白是在节点中鉴定出的首个不对称信号[1][2]。该信号通路的下游是左侧特异性基因Nodal、Lefty-1、Lefty-2和Pitx2[1][3][4][5]。在右侧身体，激活素信号通路的功能通过cActRIIa的右侧表达得以体现[1][6]。我们检测到脊椎动物发育中的另一个关键分子，成纤维细胞生长因子8（FGF8）[7][8]，在后节点右侧不对称表达。我们证明FGF8的转录由激活素诱导，且FGF8蛋白抑制Nodal和Pitx2的表达，并导致鸡类蜗牛相关基因（cSnR）的表达。在左侧应用FGF8会使心脏环化方向随机化。
