Long range regulation of the sonic hedgehog gene

The regulatory architecture that controls developmental genes is often a collection of enhancers that, in combination, generate a complex spatial and temporal pattern of expression. These enhancers populate domains operating at long distances and, in the case of the sonic hedgehog ( Shh ) locus, this regulatory domain covers ∼900–1000 kb. Within this context each embryonic tissue that expresses Shh has acquired its own regulatory apparatus which may require the activity from several distinct enhancers. Expression of Shh in the developing limb bud is driven by a single enhancer that interprets a myriad of genetic information to initiate expression in the posterior margin of the limb bud, inhibits expression along the anterior margin, defines the level of expression, and sets the tissue boundary of expression.