(A) Expression of the Sonic hedgehog gene in a 4-day chick embryo, shown by in situ hybridization (dorsal view of the trunk at the level of the wing buds). The gene is expressed in the midline of the body and at the posterior border (the polarizing region) of each of the two wing buds. Sonic hedgehog protein spreads out from these sources. (B) Normal wing development. (C) A graft of tissue from the polarizing region causes a mirror-image duplication of the pattern of the host wing. The type of digit that develops is thought to be dictated by the local concentration of Sonic hedgehog protein; different types of digit (labeled 2, 3, and 4) therefore form according to their distance from a source of Sonic hedgehog. (A, courtesy of Randall S. Johnson and Robert D. Riddle.)