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Human notochordal process and notochordal canal (Carnegie stage 8)

The notochord (axial mesoderm, notochordal process) is the defining structure forming in all chordate embryos (taxonomic rank: phylum Chordata). It is an early forming midline structure in the trilaminar embryo mesoderm layer initially ventral to the ectoderm, then neural plate and finally neural tube. This is a transient embryonic anatomy structure, not existing in the adult, required for patterning the surrounding tissues. The patterning signal secreted by notochord cells is sonic hedgehog (shh). This secreted protein binds to receptors on target cells activating a signaling pathway involved in that tissues differentiation and development. This response appears to be concentration dependent, that is the closer to the notochord the higher the shh concentration.

Thought to have at least 2 early roles in development and later roles in patterning surrounding tissues. 1. Mechanical, influencing the folding of the early embryo; 2. Morphogenic, secreting sonic hedgehog a protein which regulates the development of surrounding tissues (neural plate, somites, endoderm and other organs).

In humans, the notochord forms in week 3, is eventually lost from vertebral regions and contributes to the nucleus pulposus of the intervertebral disc during the formation of the vertebral column.

Links: Lecture - Week 3 | Sonic hedgehog | Week 3 | stage 7 | stage 8 | Epithelial Mesenchymal Transition | Notochord | Development Animation - Notochord | Neural | Axial Skeleton | Musculoskeletal | Gastrulation | Category:Notochord

Some Recent Findings

Notochord secreting sonic hedgehog (shown in white)
  • Mechanical control of notochord morphogenesis by extra-embryonic tissues in mouse embryos[1] "Here, we show that in mouse embryos, the expansion of the amniotic cavity (AC), which is formed between embryonic and extraembryonic tissues, provides the mechanical forces required for a type of morphogenetic movement of the notochord known as convergent extension (CE) in which the cells converge to the midline and the tissue elongates along the antero-posterior (AP) axis. The notochord is stretched along the AP axis, and the expansion of the AC is required for CE. Both mathematical modeling and physical simulation showed that a rectangular morphology of the early notochord caused the application of anisotropic force along the AP axis to the notochord through the isotropic expansion of the AC. AC expansion acts upstream of planar cell polarity (PCP) signaling, which regulates CE movement. Our results highlight the importance of extraembryonic tissues as a source of the forces that control the morphogenesis of embryos."
  • Transcriptional profiling of the nucleus pulposus: say yes to notochord[2]"This editorial addresses the debate concerning the origin of adult nucleus pulposus cells in the light of profiling studies by Minogue and colleagues. In their report of several marker genes that distinguish nucleus pulposus cells from other related cell types, the authors provide novel insights into the notochordal nature of the former. Together with recently published work, their work lends support to the view that all cells present within the nucleus pulposus are derived from the notochord. Hence, the choice of an animal model for disc research should be based on considerations other than the cell loss and replacement by non-notochordal cells."
  • Notochord-derived BMP antagonists inhibit endothelial cell generation and network formation[3] "Embryonic blood vessel formation is initially mediated through the sequential differentiation, migration, and assembly of endothelial cells (ECs). ...We have previously shown that the notochord is responsible for the generation and maintenance of the avascular midline and that BMP antagonists expressed by this embryonic tissue, including Noggin and Chordin, can mimic this inhibitory role. Here we report that the notochord suppresses the generation of ECs from the mesoderm both in vivo and in vitro."
More recent papers  
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches

Search term: Notochord

Susan Wopat, Jennifer Bagwell, Kaelyn D Sumigray, Amy L Dickson, Leonie F A Huitema, Kenneth D Poss, Stefan Schulte-Merker, Michel Bagnat Spine Patterning Is Guided by Segmentation of the Notochord Sheath. Cell Rep: 2018, 22(8);2026-2038 PubMed 29466731

Jun Aruga Zic Family Proteins in Emerging Biomedical Studies. Adv. Exp. Med. Biol.: 2018, 1046;233-248 PubMed 29442325

Heike Kroeger, Neil Grimsey, Ryan Paxman, Wei-Chieh Chiang, Lars Plate, Ying Jones, Peter X Shaw, JoAnn Trejo, Stephen H Tsang, Evan Powers, Jeffery W Kelly, R Luke Wiseman, Jonathan H Lin The unfolded protein response regulator ATF6 promotes mesodermal differentiation. Sci Signal: 2018, 11(517); PubMed 29440509

Stanislav Kremnyov, Kristine Henningfeld, Christoph Viebahn, Nikoloz Tsikolia Divergent axial morphogenesis and early shh expression in vertebrate prospective floor plate. Evodevo: 2018, 9;4 PubMed 29423139

Kuder Reshma Shabnam, Gundala Harold Philip Developmental toxicity of Deltamethrin and 3-Phenoxybenzoic acid in embryo-larval stages of Zebrafish (Danio rerio). Toxicol. Mech. Methods: 2018;1-25 PubMed 29421951

Notochord Development

Stage8 sem1.jpg Human Embryo notochordal plate

A scanning electron micrograph (SEM) image of the human embryo (stage 8, day 15).

The notochordal plate is the initial early transient cellular structure and region lying above the primitive streak, that will later be converted into the notochord.

Click Here to play on mobile device

This animation shows the early development of the notochord occurring during week 3 of human development.

This is a dorsal view of the embryonic disc, caudal (tail and connecting stalk end) to the bottom and rostral (head end) to the top. The indentations show the location of the cloacal (bottom) and buccopharyngeal (top) membranes. The raised region in the middle of the embryonic disc is the primitive node (Hensen's node).

The right hand side of the gastrulating embryonic disc is removed to the midline to show the the position of the initial axial process (purple). As the animation plays the axial process extends rostrally from the primitive node towards the buccopharyngeal membrane, where it stops.

A cross-section view above the primitive node is shown in the second animation below.

Grey - epiblast forming ectoderm | Yellow - endoderm | Orange - mesderm | Purple - axial process

Links: MP4 version | Quicktime version | Notochord Movie

Click Here to play on mobile device

This animation shows the early development of the notochord in relation to the endoderm in the trilaminar embryo.

The view is a cross-section showing how the axial process initially is formed, then fused with the endoderm, to finally separate as a midline mesoderm structure.

Yellow - endoderm | Purple - axial process

Links: MP4 version | Notochord Movie


Neuralplate cartoon.png Somite cartoon5.png
Neural tube patterning Somite patterning


Week 4

Stage11 sem100.jpg

Human embryo 25 days, 19 somite pairs Scanning EM. (Carnegie stage 11)

Week 8

Stage22 vertebra and spinal cord 1.jpg

Vertebra and Spinal cord (Carnegie Stage 22)

Nucleus Pulposus


Ossification endochondral 1c.jpg

Mouse Notochord

Mouse (E11) Notochord labeling HNF3beta[4]
Mouse embryo E11 HNF3beta notochord marker 02.jpg Mouse embryo E11 HNF3beta notochord marker 03.jpg Mouse embryo E11 HNF3beta notochord marker 04.jpg
  • nc; notochord, fp; floor plate.
  • lb; lung bud, hg; hindgut, st; stomach.
  • HNF3beta - FORKHEAD BOX A2 (FOXA2) Hepatocyte nuclear factor 3β (HNF3β)

Links: Image 1 - E11 Notochord | Image 2 - E11 Notochord | Image 3 - E11 Notochord | Image 4 - E11 Notochord | Notochord | Mouse Development | Category:Mouse E11.0 | Image- Mouse embryo E11 and tomography | Image - Mouse embryo E11 tomography | OMIM FORKHEAD BOX A2

Molecular Factors

Xenopus FoxA4 model
Xenopus FoxA4 model[5]


Abnormalities include remnants of notochord that fail to regress. Locations can be along the embryonic path of the notochord and include: ecchordosis physaliphora, odontoid process of the axis, and in the coccyx. Less common locations are in the nasopharynx (Tornwaldt's cysts).

Ecchordosis physaliphora

Benign ectopic nests found along the craniospinal axis forming from notochordal remnants.[6]

Ecchordosis physaliphora radiography.jpg

Brain radiography showing (A) Axial CTA (bone window); (B) Sagittal T1 MRI; (C) Sagittal T2 MRI showing EP and pontine telangiectasia; (D) CTA showing fenestrated basilar artery.[6]

Tornwaldt's cysts

A rare nasopharyngeal lesion occurring in humans thought to develop from remnants of the embryonic notochord adjacent with the embryonic foregut.[7][8] These cysts are covered by the nasopharynx mucous membrane. Named after Gustav Ludwig Tornwaldt (1843 - 1910) a German physician, the name is also spelled Thornwaldt.


Rare type of bone cancer arising from remnants of the embryonic notochord (for review see[9]) Nearly all chordomas express the T-box transcription factor brachyury.

Links: Tbx | OMIM Chordoma | chordoma foundation


  1. Yu Imuta, Hiroshi Koyama, Dongbo Shi, Mototsugu Eiraku, Toshihiko Fujimori, Hiroshi Sasaki Mechanical control of notochord morphogenesis by extra-embryonic tissues in mouse embryos. Mech. Dev.: 2014, 132;44-58 PubMed 24509350
  2. Irving M Shapiro, Makarand V Risbud Transcriptional profiling of the nucleus pulposus: say yes to notochord. Arthritis Res. Ther.: 2010, 12(3);117 PubMed 20497604
  3. Michael Bressan, Patricia Davis, John Timmer, Doris Herzlinger, Takashi Mikawa Notochord-derived BMP antagonists inhibit endothelial cell generation and network formation. Dev. Biol.: 2009, 326(1);101-11 PubMed 19041859
  4. Piotr Hajduk, Hideaki Sato, Prem Puri, Paula Murphy Abnormal notochord branching is associated with foregut malformations in the adriamycin treated mouse model. PLoS ONE: 2011, 6(11);e27635 PubMed 22132119 | PLoS One.
  5. Sabrina Murgan, Aitana Manuela Castro Colabianchi, Renato José Monti, Laura Elena Boyadjián López, Cecilia E Aguirre, Ernesto González Stivala, Andrés E Carrasco, Silvia L López FoxA4 Favours Notochord Formation by Inhibiting Contiguous Mesodermal Fates and Restricts Anterior Neural Development in Xenopus Embryos. PLoS ONE: 2014, 9(10);e110559 PubMed 25343614 | PLoS ONE
  6. 6.0 6.1 Carlito Lagman, Kunal Varshneya, J Manuel Sarmiento, Alan R Turtz, Rohan V Chitale Proposed Diagnostic Criteria, Classification Schema, and Review of Literature of Notochord-Derived Ecchordosis Physaliphora. Cureus: 2016, 8(3);e547 PubMed 27158576
  7. H Miyahara, T Matsunaga Tornwaldt's disease. Acta Otolaryngol Suppl: 1994, 517;36-9 PubMed 7856446
  8. Marcus W Moody, David H Chi, David M Chi, John C Mason, C Douglas Phillips, Charles W Gross, Rodney J Schlosser Tornwaldt's cyst: incidence and a case report. Ear Nose Throat J: 2007, 86(1);45-7, 52 PubMed 17315835
  9. Sukru Gulluoglu, Ozlem Turksoy, Aysegul Kuskucu, Ugur Ture, Omer Faruk Bayrak The molecular aspects of chordoma. Neurosurg Rev: 2015; PubMed 26363792


Makarand V Risbud, Irving M Shapiro Notochordal cells in the adult intervertebral disc: new perspective on an old question. Crit. Rev. Eukaryot. Gene Expr.: 2011, 21(1);29-41 PubMed 21967331

Makarand V Risbud, Thomas P Schaer, Irving M Shapiro Toward an understanding of the role of notochordal cells in the adult intervertebral disc: from discord to accord. Dev. Dyn.: 2010, 239(8);2141-8 PubMed 20568241

Derek L Stemple Structure and function of the notochord: an essential organ for chordate development. Development: 2005, 132(11);2503-12 PubMed 15890825

| Development


Yu Imuta, Hiroshi Koyama, Dongbo Shi, Mototsugu Eiraku, Toshihiko Fujimori, Hiroshi Sasaki Mechanical control of notochord morphogenesis by extra-embryonic tissues in mouse embryos. Mech. Dev.: 2014, 132;44-58 PubMed 24509350

Casey L Korecki, Juan M Taboas, Rocky S Tuan, James C Iatridis Notochordal cell conditioned medium stimulates mesenchymal stem cell differentiation toward a young nucleus pulposus phenotype. Stem Cell Res Ther: 2010, 1(2);18 PubMed 20565707

Helena E Christiansen, Michael R Lang, James M Pace, David M Parichy Critical early roles for col27a1a and col27a1b in zebrafish notochord morphogenesis, vertebral mineralization and post-embryonic axial growth. PLoS ONE: 2009, 4(12);e8481 PubMed 20041163

Melissa A Edeling, Subramaniam Sanker, Takaki Shima, P K Umasankar, Stefan Höning, Hye Y Kim, Lance A Davidson, Simon C Watkins, Michael Tsang, David J Owen, Linton M Traub Structural requirements for PACSIN/Syndapin operation during zebrafish embryonic notochord development. PLoS ONE: 2009, 4(12);e8150 PubMed 19997509

Jeffrey D Lee, Kathryn V Anderson Morphogenesis of the node and notochord: the cellular basis for the establishment and maintenance of left-right asymmetry in the mouse. Dev. Dyn.: 2008, 237(12);3464-76 PubMed 18629866

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