ArticleNature communications2023
Hedgehog is relayed through dynamic heparan sulfate interactions to shape its gradient.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Mechanistic trade-offs between local and long-range signaling activity in natural and synthetic morphogens.Science advances · 2026Article
- Emerging evidence for a cooperative pathway of Hedgehog release.Nature reviews. Molecular cell biology · 2026Article
- Extracellular matrix remodelling in neurological diseases.Nature reviews. Neurology · 2026Review
- A long-chain heparan sulfate capture mechanism directs paracrine GDNF-GFRα1 signalling through RET.bioRxiv : the preprint server for biology · 2026Article
- Scube2 primes Dispatched and ADAM10-mediated Shh release by recruiting HDL acceptors to the plasma membrane.Communications biology · 2026Article
- SULF1 in Cancer Associated Fibroblasts Promotes Invasion in Head and Neck Cancer Cell Lines.Cancer medicine · 2026Article
- The Role of the Hedgehog Pathway in Alcohol-Induced Birth Defects.Advances in experimental medicine and biology · 2026Review
- A guide to building the matrisome interactome: from computational predictions to experimental validation.The FEBS journal · 2026Review
- Mechanistic adaptation of the metazoan RabGEFs Mon1-Ccz1 and Fuzzy-Inturned.Science advances · 2025Article
- Molecularly Defined Glycocalyx Models Reveal ABJACS Au · 2025Article
- Evolution of SARS-CoV-2 spike trimers towards optimized heparan sulfate cross-linking and inter-chain mobility.Scientific reports · 2024Article
- Interactions of proteins with heparan sulfate.Essays in biochemistry · 2024Review
- Synthetically programming natural cell-cell communication pathways for tissue engineering.Current opinion in biomedical engineering · 2024Article
- Identification of small molecule antagonists of sonic hedgehog/heparin binding with activity in hedgehog functional assays.Biochimica et biophysica acta. General subjects · 2024Article
- Review
- The role of glycosaminoglycan modification in Hedgehog regulated tissue morphogenesis.Biochemical Society transactions · 2023Review
- Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cellular differentiation is directly determined by concentration gradients of morphogens. As a central model for gradient formation during development, Hedgehog (Hh) morphogens spread away from their source to direct growth and pattern formation in Drosophila wing and eye discs. What is not known is how extracellular Hh spread is achieved and how it translates into precise gradients. Here we show that two separate binding areas located on opposite sides of the Hh molecule can interact directly and simultaneously with two heparan sulfate (HS) chains to temporarily cross-link the chains. Mutated Hh lacking one fully functional binding site still binds HS but shows reduced HS cross-linking. This, in turn, impairs Hhs ability to switch between both chains in vitro and results in striking Hh gradient hypomorphs in vivo. The speed and propensity of direct Hh switching between HS therefore shapes the Hh gradient, revealing a scalable design principle in morphogen-patterned tissues.
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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.