ArticleDevelopmental cell2022
Sonic hedgehog is not a limb morphogen but acts as a trigger to specify all digits in mice.
Article in Developmental cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 39 citations in OpenAlex.
- MEGF8 controls osteogenic differentiation through post-transcriptional regulation of BMP-SMAD signaling in craniosynostosis.Cell death and differentiation · 2026Article
- Posterior shift of Shh-Fgf signaling in axolotl limb regeneration drives sequential digit formation.iScience · 2026Article
- Evolution of limb and digit identity genes since the tetrapod ancestor.Nature communications · 2026Article
- WATER reveals heterochrony of molecular programs underlies developmental failure caused by minor spliceosome inhibition.bioRxiv : the preprint server for biology · 2026Article
- A characterization of axolotl digit regeneration: conserved mechanisms, divergent patterning, and a critical role for hedgehog signaling.NPJ Regenerative medicine · 2026Article
- Temporal constraints on enhancer usage shape the regulation of limb gene transcription.Nature communications · 2026Article
- Proximal phalanges of digit 1 have different identities in the forelimbs and hindlimbs of the mouse.Scientific reports · 2025Article
- Dual Bmp-negative feedback loops modulate function of both AER and ZPA to buffer and constrain postaxial digit number.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Caudal fin shape imprinted during late zebrafish embryogenesis is re-patterned by the Sonic hedgehog pathway.PLoS biology · 2025Article
- Article
- WNT signaling coordinately controls mouse limb bud outgrowth and establishment of the digit-interdigit pattern.Development (Cambridge, England) · 2025Article
- Thalidomide-induced limb malformations: an update and reevaluation.Archives of toxicology · 2025Review
- Single-cell profiling of penta- and tetradactyl mouse limb buds identifies mesenchymal progenitors controlling digit numbers and identities.Nature communications · 2025Article
- Loss of Sc5d results in micrognathia due to a failure in osteoblast differentiation.Journal of advanced research · 2024Article
- A dominant missense variant within LMBR1 related to equine polydactyly.Communications biology · 2024Article
- Morphogens in the evolution of size, shape and patterning.Development (Cambridge, England) · 2024Review
- The development of hair follicles and nail.Developmental biology · 2024Review
- Insights into digit evolution from a fate map study of the forearm using Chameleon, a new transgenic chicken line.Development (Cambridge, England) · 2024Article
- TBX3 is essential for establishment of the posterior boundary of anterior genes and upregulation of posterior genes together with HAND2 during the onset of limb bud development.Development (Cambridge, England) · 2024Article
- Tgfbr1 controls developmental plasticity between the hindlimb and external genitalia by remodeling their regulatory landscape.Nature communications · 2024Article
Corrections and comments
- Commented on by
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.