| First Author | Zhu J | Year | 2022 |
| Journal | Dev Cell | Volume | 57 |
| Issue | 17 | Pages | 2048-2062.e4 |
| PubMed ID | 35977544 | Mgi Jnum | J:328557 |
| Mgi Id | MGI:7336661 | Doi | 10.1016/j.devcel.2022.07.016 |
| Citation | Zhu J, et al. (2022) Sonic hedgehog is not a limb morphogen but acts as a trigger to specify all digits in mice. Dev Cell 57(17):2048-2062.e4 |
| abstractText | 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. |
