Sonic Hedgehog is not a limb morphogen but acts as a trigger to specify all digits.

Limb patterning by Sonic hedgehog (Shh) has served as a paradigm of "morphogen" function, acting either by graded spatial or temporal signal integration. Yet how Shh instructs distinct digit identities remains controversial. Here, we bypassed the requirement for Shh in cell survival during limb bud outgrowth and demonstrate that a transient, early Shh pulse is both necessary and sufficient for normal limb development. Our analysis of Shh-responding cells shows signaling acts at only short-range during this time window and that Shh patterns digits indirectly, via a relay mechanism, rather than by direct spatial or temporal signal integration. Using a genetic assay for relay signaling, we unexpectedly discovered Shh also specifies digit 1 (the thumb; previously thought to be exclusively Shh-independent) indirectly, thus implicating Shh in a unique regulatory hierarchy for digit 1 evolutionary adaptations, such as opposable thumbs. This study illuminates Shh as a trigger for a relay network that becomes rapidly self-sustaining, with mechanistic relevance for limb development, regeneration, and evolution.