ArticleProceedings of the National Academy of Sciences of the United States of America2011
Hedgehog signaling is required for formation of the notochord sheath and patterning of nuclei pulposi within the intervertebral discs.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed, 144 citations in OpenAlex.
- CRISPR activation reveals SOX5/6/9 as key transcriptional regulators directing iPSC-derived cells toward a notochordal lineage.Stem cell reports · 2026Article
- Proteomic Atlas of Notochordal Cell-Derived Extracellular Vesicles Highlights EV-Specific NF-κB Modulation and Functional Implications of the Protein Corona.Journal of extracellular biology · 2026Article
- Surviving the Nucleus Pulposus Desert: Next-Generation Strategies for Intervertebral Disc Cell Therapy.JOR spine · 2026Article
- Article
- The notochord: development, disease and stem cell-based modelling.Development (Cambridge, England) · 2026Review
- Dasatinib and quercetin senolytic treatment delays early onset intervertebral disc degeneration in SM/J mice.Bone research · 2026Article
- The role of genetics and molecular mechanisms in early onset scoliosis.Journal of clinical orthopaedics and trauma · 2026Review
- EVC protein regulates Sonic hedgehog signaling during human intervertebral disc development and degeneration.iScience · 2026Article
- The TBXT rs2305089 SNP links the benign notochordal cell tumour and chordoma.The Journal of pathology · 2025Article
- Dasatinib and quercetin senolytic treatment delays early onset intervertebral disc degeneration in SM/J mice.Research square · 2025Article
- Proteomic profiling of small extracellular vesicles from bovine nucleus pulposus cells.PloS one · 2025Article
- Spinal scoliosis: insights into developmental mechanisms and animal models.Spine deformity · 2025Review
- Planar cell polarity zebrafish models of congenital scoliosis reveal underlying defects in notochord morphogenesis.Development (Cambridge, England) · 2024Article
- Getting to the Core: Exploring the Embryonic Development from Notochord to Nucleus Pulposus.Journal of developmental biology · 2024Review
- A Spatio-Temporal-Dependent Requirement of Sonic Hedgehog in the Early Development of Sclerotome-Derived Vertebrae and Ribs.International journal of molecular sciences · 2024Article
- Intervertebral disc-intrinsic Hedgehog signaling maintains disc cell phenotypes and prevents disc degeneration through both cell autonomous and non-autonomous mechanisms.Cellular and molecular life sciences : CMLS · 2024Article
- Notochordal cells: A potential therapeutic option for intervertebral disc degeneration.Cell proliferation · 2024Review
- Review
- Recommendations for intervertebral disc notochordal cell investigation: From isolation to characterization.JOR spine · 2023Article
- Development and Degeneration of the Intervertebral Disc-Insights from Across Species.Veterinary sciences · 2023Review
43 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
The vertebrae notochord is a transient rod-like structure that produces secreted factors that are responsible for patterning surrounding tissues. During later mouse embryogenesis, the notochord gives rise to the middle part of the intervertebral disc, called the nucleus pulposus. Currently, very little is known about the molecular mechanisms responsible for forming the intervertebral discs. Here we demonstrate that hedgehog signaling is required for formation of the intervertebral discs. Removal of hedgehog signaling in the notochord and nearby floorplate resulted in the formation of an aberrant notochord sheath that normally surrounds this structure. In the absence of the notochord sheath, small nuclei pulposi were formed, with most notochord cells dispersed throughout the vertebral bodies during embryogenesis. Our data suggest that the formation of the notochord sheath requires hedgehog signaling and that the sheath is essential for maintaining the rod-like structure of the notochord during early embryonic development. As notochord cells form nuclei pulposi, we propose that the notochord sheath functions as a "wrapper" around the notochord to constrain these cells along the vertebral column.
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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.