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Notochord

Anatomy and Physiology · NLM MeSH · updated 2026-10-31 · version 1

Citations verified against PubMedNot yet clinician-reviewed10 referencesApproximately 4 min read

A cartilaginous rod of mesodermal cells at the dorsal midline of all chordate embryos.

Table of Contents

1. Definition2. Research landscape3. Reading the evidence4. Open-access studies5. Key reviews6. References7. About this article

Definition and research guide

This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.

Content available: 4 complete abstracts (677 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.

Definition

A cartilaginous rod of mesodermal cells at the dorsal midline of all chordate embryos. In lower vertebrates, notochord is the backbone of support. In the higher vertebrates, notochord is a transient structure, and segments of the vertebral column will develop around it. Notochord is also a source of midline signals that pattern surrounding tissues including the neural tube development.

Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.

Also known as: Notochords; Chordamesoderm; Chordamesoderms.

Where it fits in the MeSH classification

Broader topics
Embryonic Structures

Related concepts

  • Chordate
  • Neural Tube

Research landscape

PubMed indexes 1,779 records tagged with the MeSH heading “Notochord” (counts retrieved 2026-10-31). 173 of them (9.7%) were published from 2020 onward, and the busiest period so far is through 1999 with 686 records.

Reviews account for 161 records (9.1%) and meta-analyses for 0. Randomized controlled trials number 0 (0.0%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.

PubMed records by publication periodthrough 1999: 686 records; 2000-2009: 486 records; 2010-2019: 434 records; 2020 onward: 173 records686through 19994862000-20094342010-20191732020 onward
Records in PubMed indexed with this heading, by publication period. Real counts from NCBI E-utilities; the final period covers only part of the current year. Volume reflects how much has been published, not how strong the evidence is.
Show the data
PeriodRecords
through 1999686
2000-2009486
2010-2019434
2020 onward173
Share of records by publication typeReviews: 9.1 percent; Meta-analyses: 0.0 percent; Randomized controlled trials: 0.0 percentReviews9.1% (161)Meta-analyses0.0% (0)Randomized controlled trials0.0% (0)
Share of all PubMed records on this heading that carry each publication type. Types overlap with other records, so the shares do not sum to 100%.
Publication-type chart data
Publication types among 1,779 PubMed records
TypeRecordsShare
Reviews1619.1%
Meta-analyses00.0%
Randomized controlled trials00.0%

Method: PubMed query "Notochord"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.

Reading the evidence in anatomy and physiology

Anatomy describes how body structures are built and physiology describes how they normally work, so most findings here are descriptive or mechanistic rather than evidence about treatment. Much of what is known comes from dissection, imaging, tissue studies and experiments in animals, and measurements in healthy volunteers can differ from those in people with disease or at different ages. Normal ranges vary between individuals and populations. Check whether a result was measured in people or in another species, the age and health of the participants, and the method used.

Evidence from open-access studies

These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.

Study comparison — selected abstracts, not a systematic review
Study / authorsYearSource label / designEurope PMC citationsLicence / source
Damage-induced reactive oxygen species enable zebrafish tail regeneration by repositioning of Hedgehog expressing cells
Romero MMG, McCathie G, Jankun P, Roehl HH
2018Research article
Design not recorded in structured metadata
81cc by
PMID 30275454 · DOI · PMC6167316
Segmentation of the zebrafish axial skeleton relies on notochord sheath cells and not on the segmentation clock
Lleras Forero L, Narayanan R, Huitema LF, VanBergen M, Apschner A, Peterson-Maduro J, et al.
2018Research article
Design not recorded in structured metadata
74cc by
PMID 29624170 · DOI · PMC5962341
Variable combinations of specific ephrin ligand/Eph receptor pairs control embryonic tissue separation
Rohani N, Parmeggiani A, Winklbauer R, Fagotto F
2014Research article
Design not recorded in structured metadata
67cc by
PMID 25247423 · DOI · PMC4172438
Coupling Vgll4b/Yap-regulated posterior cell addition with anterior vacuolation enables robust notochord elongation
Camacho-Macorra C, Ceccarelli AS, Serrano Nájera G, Saunders D, Boesgaard I, Chara O, et al.
2026Research article
Design not recorded in structured metadata
0cc by
PMID 42596839 · DOI · PMC13615686

Damage-induced reactive oxygen species enable zebrafish tail regeneration by repositioning of Hedgehog expressing cells [1]

Research article Romero MMG, McCathie G, Jankun P, Roehl HH · · 2018 · cited 81 times (Europe PMC)

Abstract reading summary — source excerpts
Opening excerpt
Many aquatic vertebrates have a remarkable ability to regenerate limbs and tails after amputation.
Closing excerpt
Our results provide a model for how ROS initiate tail regeneration, and indicate that developmental signalling pathways can play regenerative functions that are not directly related to their developmental roles.
Interpretation limits
Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (149 words)

Many aquatic vertebrates have a remarkable ability to regenerate limbs and tails after amputation. Previous studies indicate that reactive oxygen species (ROS) signalling initiates regeneration, but the mechanism by which this takes place is poorly understood. Developmental signalling pathways have been shown to have proregenerative roles in many systems. However, whether these are playing roles that are specific to regeneration, or are simply recapitulating their developmental functions is unclear. Here, we analyse zebrafish larval tail regeneration and find evidence that ROS released upon wounding cause repositioning of notochord cells to the damage site. These cells secrete Hedgehog ligands that are required for regeneration. Hedgehog signalling is not required for normal tail development suggesting that it has a regeneration-specific role. Our results provide a model for how ROS initiate tail regeneration, and indicate that developmental signalling pathways can play regenerative functions that are not directly related to their developmental roles.

Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 30275454 · DOI · PMC6167316

Segmentation of the zebrafish axial skeleton relies on notochord sheath cells and not on the segmentation clock [2]

Research article Lleras Forero L, Narayanan R, Huitema LF, VanBergen M, Apschner A, Peterson-Maduro J, et al. · · 2018 · cited 74 times (Europe PMC)

Abstract reading summary — source excerpts
Opening excerpt
Segmentation of the axial skeleton in amniotes depends on the segmentation clock, which patterns the paraxial mesoderm and the sclerotome.
Closing excerpt
This behavior is not consistent with a clock-type mechanism in the notochord.
Interpretation limits
Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (142 words)

Segmentation of the axial skeleton in amniotes depends on the segmentation clock, which patterns the paraxial mesoderm and the sclerotome. While the segmentation clock clearly operates in teleosts, the role of the sclerotome in establishing the axial skeleton is unclear. We severely disrupt zebrafish paraxial segmentation, yet observe a largely normal segmentation process of the chordacentra. We demonstrate that axial entpd5+ notochord sheath cells are responsible for chordacentrum mineralization, and serve as a marker for axial segmentation. While autonomous within the notochord sheath, entpd5 expression and centrum formation show some plasticity and can respond to myotome pattern. These observations reveal for the first time the dynamics of notochord segmentation in a teleost, and are consistent with an autonomous patterning mechanism that is influenced, but not determined by adjacent paraxial mesoderm. This behavior is not consistent with a clock-type mechanism in the notochord.

Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 29624170 · DOI · PMC5962341

Variable combinations of specific ephrin ligand/Eph receptor pairs control embryonic tissue separation [3]

Research article Rohani N, Parmeggiani A, Winklbauer R, Fagotto F · · 2014 · cited 67 times (Europe PMC)

Abstract reading summary — source excerpts
Opening excerpt
Ephrins and Eph receptors are involved in the establishment of vertebrate tissue boundaries.
Closing excerpt
These results provide a paradigm for how developmental systems may integrate multiple cues to generate discrete local outcomes.
Interpretation limits
Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (203 words)

Ephrins and Eph receptors are involved in the establishment of vertebrate tissue boundaries. The complexity of the system is puzzling, however in many instances, tissues express multiple ephrins and Ephs on both sides of the boundary, a situation that should in principle cause repulsion between cells within each tissue. Although co-expression of ephrins and Eph receptors is widespread in embryonic tissues, neurons, and cancer cells, it is still unresolved how the respective signals are integrated into a coherent output. We present a simple explanation for the confinement of repulsion to the tissue interface: Using the dorsal ectoderm-mesoderm boundary of the Xenopus embryo as a model, we identify selective functional interactions between ephrin-Eph pairs that are expressed in partial complementary patterns. The combined repulsive signals add up to be strongest across the boundary, where they reach sufficient intensity to trigger cell detachments. The process can be largely explained using a simple model based exclusively on relative ephrin and Eph concentrations and binding affinities. We generalize these findings for the ventral ectoderm-mesoderm boundary and the notochord boundary, both of which appear to function on the same principles. These results provide a paradigm for how developmental systems may integrate multiple cues to generate discrete local outcomes.

Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 25247423 · DOI · PMC4172438

Coupling Vgll4b/Yap-regulated posterior cell addition with anterior vacuolation enables robust notochord elongation [4]

Research article Camacho-Macorra C, Ceccarelli AS, Serrano Nájera G, Saunders D, Boesgaard I, Chara O, et al. · · 2026

Abstract reading summary — source excerpts
Opening excerpt
Robust tissue growth control requires long-range communication between the rate of progenitor addition and tissue expansion.
Closing excerpt
These results support a long-range feedback mechanism linking progenitor recruitment to vacuolation, enabling the notochord to balance cellular input with volumetric expansion, thereby maintaining tissue proportions.
Interpretation limits
Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (183 words)

Robust tissue growth control requires long-range communication between the rate of progenitor addition and tissue expansion. However, the regulatory mechanisms that couple these processes are unknown. In zebrafish, notochord morphogenesis is a driver of axis extension through both posterior progenitor addition and anterior vacuolation. To elucidate how progenitor dynamics and vacuole-driven cell expansion interact to elongate the notochord, we generated a mathematical model linking progenitor addition rate to the expansion of cells from anterior to posterior to simulate vacuolation rate. Comparing this with empirical measurements, we find that progenitor incorporation, together with vacuolation, produces a linear gradient in nearest neighbour distance. We next explored the role of YAP/TAZ in regulating progenitor addition in mutants for the YAP/TAZ inhibitor vgll4b. We find that vgll4b expression and YAP activity are enriched in posterior midline progenitors. Loss of vgll4b elevates YAP signalling, enhances progenitor addition, restricts vacuole expansion, and - after a transient buffering phase - compromises anterior-posterior axis elongation. These results support a long-range feedback mechanism linking progenitor recruitment to vacuolation, enabling the notochord to balance cellular input with volumetric expansion, thereby maintaining tissue proportions.

Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42596839 · DOI · PMC13615686

Key reviews and meta-analyses

The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.

  • Research article Structure and function of the notochord: an essential organ for chordate development [5]
    Stemple DL · Development · 2005 · cited 344 times (Europe PMC)
  • Research article The notochordal cell in the nucleus pulposus: a review in the context of tissue engineering [6]
    Hunter CJ, Matyas JR, Duncan NA · Tissue Eng · 2003 · cited 227 times (Europe PMC)
  • Research article Notochordal cells in the adult intervertebral disc: new perspective on an old question [7]
    Risbud MV, Shapiro IM · Crit Rev Eukaryot Gene Expr · 2011 · cited 137 times (Europe PMC)
  • Research article Toward an understanding of the role of notochordal cells in the adult intervertebral disc: from discord to accord [8]
    Risbud MV, Schaer TP, Shapiro IM · Dev Dyn · 2010 · cited 116 times (Europe PMC)
  • Research article Morphogenesis of the node and notochord: the cellular basis for the establishment and maintenance of left-right asymmetry in the mouse [9]
    Lee JD, Anderson KV · Dev Dyn · 2008 · cited 109 times (Europe PMC)
  • Research article The role of the notochord and floor plate in inductive interactions [10]
    Placzek M · Curr Opin Genet Dev · 1995 · cited 105 times (Europe PMC)

References

  1. Romero MMG, McCathie G, Jankun P, Roehl HH. Damage-induced reactive oxygen species enable zebrafish tail regeneration by repositioning of Hedgehog expressing cells. . 2018. PMID 30275454 · DOI · PMC6167316
  2. Lleras Forero L, Narayanan R, Huitema LF, VanBergen M, Apschner A, Peterson-Maduro J, et al.. Segmentation of the zebrafish axial skeleton relies on notochord sheath cells and not on the segmentation clock. . 2018. PMID 29624170 · DOI · PMC5962341
  3. Rohani N, Parmeggiani A, Winklbauer R, Fagotto F. Variable combinations of specific ephrin ligand/Eph receptor pairs control embryonic tissue separation. . 2014. PMID 25247423 · DOI · PMC4172438
  4. Camacho-Macorra C, Ceccarelli AS, Serrano Nájera G, Saunders D, Boesgaard I, Chara O, et al.. Coupling Vgll4b/Yap-regulated posterior cell addition with anterior vacuolation enables robust notochord elongation. . 2026. PMID 42596839 · DOI · PMC13615686
  5. Stemple DL. Structure and function of the notochord: an essential organ for chordate development. Development. 2005. PMID 15890825 · DOI
  6. Hunter CJ, Matyas JR, Duncan NA. The notochordal cell in the nucleus pulposus: a review in the context of tissue engineering. Tissue Eng. 2003. PMID 13678445 · DOI
  7. Risbud MV, Shapiro IM. Notochordal cells in the adult intervertebral disc: new perspective on an old question. Crit Rev Eukaryot Gene Expr. 2011. PMID 21967331 · DOI · PMC3187872
  8. Risbud MV, Schaer TP, Shapiro IM. Toward an understanding of the role of notochordal cells in the adult intervertebral disc: from discord to accord. Dev Dyn. 2010. PMID 20568241 · DOI · PMC3634351
  9. Lee JD, Anderson KV. Morphogenesis of the node and notochord: the cellular basis for the establishment and maintenance of left-right asymmetry in the mouse. Dev Dyn. 2008. PMID 18629866 · DOI · PMC2593123
  10. Placzek M. The role of the notochord and floor plate in inductive interactions. Curr Opin Genet Dev. 1995. PMID 7580143 · DOI

About this article

Sources
NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
Verification
Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
Review state
automated source verified; no human expert review has been recorded yet.
Version
1, last updated 2026-10-31.

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At a glance

1,779
PubMed records on this heading
10%
published since 2020
161
review articles
0
randomized trials
10
verified references below

Counts come from PubMed on 2026-10-31; they show how much has been written, not how strong the evidence is.

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