During limb outgrowth, Shh, Fgf4, and Fgf8 act as signals controlling limb growth and patterning. Because these genes are expressed in the limb bud and other known signalling centers, we have explored the relationships between the expression of these during mouse development using double in situ hybridization. Within the node and limb bud the expression domains of these genes contact each other, whereas in the floor plate the Fgf8 expression domain does not contact that of Shh. The relative temporal order of gene expression varies in different centers. The spatial and temporal expression of Fgf4, Fgf8, and Shh suggests that conservation of molecular mechanisms in different organizing centers as well as differences between them.