ArticleNature2016
FGF8 and SHH substitute for anterior-posterior tissue interactions to induce limb regeneration.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
What it found
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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.
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Who cites it
92 citing papers in PubMed, 171 citations in OpenAlex.
- Dynamic control of cell state transitions during tissue morphogenesis.The EMBO journal · 2026Review
- The tiger salamander as a promising alternative model organism to the axolotl for fracture healing and regenerative biology research.Anatomical record (Hoboken, N.J. : 2007) · 2026Article
- Conserved anterior/posterior tissue asymmetry encodes proximal/distal positional information during axolotl limb regeneration.Cell reports · 2026Article
- Development of whole-limb skeletal patterning through the coordination of growth and self-organization models.PLoS computational biology · 2026Article
- tBid-Mediated Genetic Ablation of Connective Tissue Cells Reveals Their Key Regulatory Function During Limb Regeneration in Axolotls.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Posterior shift of Shh-Fgf signaling in axolotl limb regeneration drives sequential digit formation.iScience · 2026Article
- A characterization of axolotl digit regeneration: conserved mechanisms, divergent patterning, and a critical role for hedgehog signaling.NPJ Regenerative medicine · 2026Article
- Dorsoventral-mediatedeLife · 2026Article
- The cellular logic of limb regeneration.eLife · 2026Article
- Intermittent intra-articular delivery of FGF8b enhances cartilage homeostasis and attenuates osteoarthritis progression.Journal of orthopaedic translation · 2026Article
- Static morphogen scaling enables proportional growth in a tissue growth model inspired by axolotl limb regeneration.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Novel Antimicrobial Protein Fibroblast Growth Factor 8 Accelerates Skin Wound Healing via Directly Inhibiting Bacteria and Activating Glycolysis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Retinoic acid breakdown is required for proximodistal positional identity during axolotl limb regeneration.Nature communications · 2025Article
- Article
- Regenerative endodontic therapy: From laboratory bench to clinical practice.Journal of advanced research · 2025Review
- Neural regulation of H3K27me3 during the induction of patterning competency in regenerating Axolotl limb cells.Communications biology · 2025Article
- Article
- Nature's Secret Neuro-Regeneration Pathway in Axolotls, Polychaetes and Planarians for Human Therapeutic Target Pathways.International journal of molecular sciences · 2024Review
- Allometry in limb regeneration and scale-invariant patterning as the basis of normal morphogenesis from different sizes of blastemas.Development (Cambridge, England) · 2024Article
- Extracellular vesicles derived from Msh homeobox 1 (Msx1)-overexpressing mesenchymal stem cells improve digit tip regeneration in an amputee mice model.Scientific reports · 2024Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In salamanders, grafting of a left limb blastema onto a right limb stump yields regeneration of three limbs, the normal limb and two 'supernumerary' limbs. This experiment and other research have shown that the juxtaposition of anterior and posterior limb tissue plus innervation are necessary and sufficient to induce complete limb regeneration in salamanders. However, the cellular and molecular basis of the requirement for anterior-posterior tissue interactions were unknown. Here we have clarified the molecular basis of the requirement for both anterior and posterior tissue during limb regeneration and supernumerary limb formation in axolotls (Ambystoma mexicanum). We show that the two tissues provide complementary cross-inductive signals that are required for limb outgrowth. A blastema composed solely of anterior tissue normally regresses rather than forming a limb, but activation of hedgehog (HH) signalling was sufficient to drive regeneration of an anterior blastema to completion owing to its ability to maintain fibroblast growth factor (FGF) expression, the key signalling activity responsible for blastema outgrowth. In blastemas composed solely of posterior tissue, HH signalling was not sufficient to drive regeneration; however, ectopic expression of FGF8 together with endogenous HH signalling was sufficient. In axolotls, FGF8 is expressed only in the anterior mesenchyme and maintenance of its expression depends on sonic hedgehog (SHH) signalling from posterior tissue. Together, our findings identify key anteriorly and posteriorly localized signals that promote limb regeneration and show that these single factors are sufficient to drive non-regenerating blastemas to complete regeneration with full elaboration of skeletal elements.
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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.