Limb patterning by Sonic hedgehog (Shh), via either graded spatial or temporal signal integration, is a paradigm for “morphogen” function, yet how Shh instructs distinct digit identities remains controversial. Here, we bypass the Shh requirement in cell survival during outgrowth and demonstrate that a transient, early Shh pulse is both necessary and sufficient for normal mouse limb development. Shh response is only short range and is limited to the Shh-expressing zone during this time window. Shh patterns digits 1–3, anterior to this zone, by an indirect mechanism rather than direct spatial or temporal signal integration. Using a genetic relay-signaling assay, we discover that Shh also specifies digit 1/thumb (thought to be exclusively Shh independent) indirectly, and this finding implicates Shh in a unique regulatory hierarchy for digit 1 evolutionary adaptations such as opposable thumbs. This study illuminates Shh as a trigger for an indirect downstream network that becomes rapidly self-sustaining, with mechanistic relevance for limb development, regeneration, and evolution.

声波刺猬 (Shh) 通过分级空间或时间信号整合进行的肢体模式是“形态发生素”功能的范例，但 Shh 如何指示不同的数字身份仍然存在争议。在这里，我们绕过了生长过程中细胞存活的Shh要求，并证明短暂的早期Shh脉冲对于正常的小鼠肢体发育来说既是必要的也是充分的。嘘反应的范围很短，并且仅限于该时间窗口内的嘘表达区。嘘通过间接机制而不是直接的空间或时间信号集成来对该区域前面的数字 1-3 进行模式化。使用遗传中继信号分析，我们发现Shh还间接指定了数字1/拇指（被认为完全独立于Shh），这一发现暗示Shh参与了数字1进化适应（例如对生拇指）的独特调节层级。这项研究表明，Shh 是间接下游网络的触发因素，该网络能够快速自我维持，与肢体发育、再生和进化具有机械相关性。