FGF8 Functions in the Specification of the Right Body Side of the Chick

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.