ArticleProceedings of the National Academy of Sciences of the United States of America2024
Diffusion barriers imposed by tissue topology shape Hedgehog morphogen gradients.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Mechanistic trade-offs between local and long-range signaling activity in natural and synthetic morphogens.Science advances · 2026Article
- Convergent mechanisms in Wnt and Hedgehog signaling.Science signaling · 2026Review
- Tissue rigidity phase transition shapes morphogen gradients.Nature cell biology · 2026Article
- Article
- Position-dependent feedback drives scaling and robustness of morphogen gradients.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- In vitro reconstitution of vertebrate Sonic Hedgehog protein cholesterolysis.bioRxiv : the preprint server for biology · 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
- Dynamical systems of fate and form in development.Seminars in cell & developmental biology · 2025Review
- A live-cell biosensor of in vivo receptor tyrosine kinase activity reveals feedback regulation of a developmental gradient.Cell reports · 2025Article
- Article
- Synthetically programming natural cell-cell communication pathways for tissue engineering.Current opinion in biomedical engineering · 2024Article
- Article
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Abstract
Animals use a small number of morphogens to pattern tissues, but it is unclear how evolution modulates morphogen signaling range to match tissues of varying sizes. Here, we used single-molecule imaging in reconstituted morphogen gradients and in tissue explants to determine that Hedgehog diffused extracellularly as a monomer, and rapidly transitioned between membrane-confined and -unconfined states. Unexpectedly, the vertebrate-specific protein SCUBE1 expanded Hedgehog gradients by accelerating the transition rates between states without affecting the relative abundance of molecules in each state. This observation could not be explained under existing models of morphogen diffusion. Instead, we developed a topology-limited diffusion model in which cell-cell gaps create diffusion barriers, which morphogens can only overcome by passing through a membrane-unconfined state. Under this model, SCUBE1 promoted Hedgehog secretion and diffusion by allowing it to transiently overcome diffusion barriers. This multiscale understanding of morphogen gradient formation unified prior models and identified knobs that nature can use to tune morphogen gradient sizes across tissues and organisms.
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