Notochord

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Introduction

Human notochordal process and notochordal canal (Carnegie stage 8)
nucleus pulposus
The developing nucleus pulposus

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).

Recent work in chicken[1] suggests that the later patterning of vertebral segmentation is driven by the somite sclerotome, a result which differs from the findings in the zebrafish model.[2]


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


Notochord Links: notochord | Lecture - Week 3 | sonic hedgehog | Week 3 | stage 7 | stage 8 | epithelial mesenchymal transition | Development Animation - Notochord | neural | axial skeleton | musculoskeletal | gastrulation | Category:Notochord
Historic Embryology - Notochord 
1902 Notochord | 1908 Mammalian notochord

Some Recent Findings

Notochord secreting sonic hedgehog (shown in white)
  • The role of the notochord in amniote vertebral column segmentation[1] "The vertebral column is segmented, comprising an alternating series of vertebrae and intervertebral discs along the head-tail axis. The vertebrae and outer portion (annulus fibrosus) of the disc are derived from the sclerotome part of the somites, whereas the inner nucleus pulposus of the disc is derived from the notochord. Here we investigate the role of the notochord in vertebral patterning through a series of microsurgical experiments in chick embryos. Ablation of the notochord causes loss of segmentation of vertebral bodies and discs. However, the notochord cannot segment in the absence of the surrounding sclerotome. To test whether the notochord dictates sclerotome segmentation, we grafted an ectopic notochord. We find that the intrinsic segmentation of the sclerotome is dominant over any segmental information the notochord may possess, and no evidence that the chick notochord is intrinsically segmented. We propose that the segmental pattern of vertebral bodies and discs in chick is dictated by the sclerotome, which first signals to the notochord to ensure that the nucleus pulposus develops in register with the somite-derived annulus fibrosus. Later, the notochord is required for maintenance of sclerotome segmentation as the mature vertebral bodies and intervertebral discs form. These results highlight differences in vertebral development between amniotes and teleosts including zebrafish, where the notochord dictates the segmental pattern. The relative importance of the sclerotome and notochord in vertebral patterning has changed significantly during evolution." chicken
  • Segmentation of the zebrafish axial skeleton relies on notochord sheath cells and not on the segmentation clock[2] "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." zebrafish
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

Vikas A Tillu, Ye-Wheen Lim, Oleksiy Kovtun, Sergey Mureev, Charles Ferguson, Michele Bastiani, Kerrie-Ann McMahon, Harriet P Lo, Thomas E Hall, Kirill Alexandrov, Brett M Collins, Robert G Parton A variable undecad repeat domain in cavin1 regulates caveola formation and stability. EMBO Rep.: 2018; PubMed 30021837

Rachel M Warga, Donald A Kane A Wilson cell origin for Kupffer's vesicle in the zebrafish. Dev. Dyn.: 2018; PubMed 30016568

Quang Tien Phan, Tamara Sipka, Catherine Gonzalez, Jean-Pierre Levraud, Georges Lutfalla, Mai Nguyen-Chi Neutrophils use superoxide to control bacterial infection at a distance. PLoS Pathog.: 2018, 14(7);e1007157 PubMed 30016370

Rabjot Rai, Joe Iwanaga, Ghaffar Shokouhi, Marios Loukas, Martin M Mortazavi, Rod J Oskouian, R Shane Tubbs A comprehensive review of the clivus: anatomy, embryology, variants, pathology, and surgical approaches. Childs Nerv Syst: 2018; PubMed 29955940

Samaneh Ghazanfari, Arie Werner, Sara Ghazanfari, James C Weaver, Theodoor H Smit Morphogenesis of aligned collagen fibers in the annulus fibrosus: Mammals versus avians. Biochem. Biophys. Res. Commun.: 2018; PubMed 29953854

Older papers  
  • Mechanical control of notochord morphogenesis by extra-embryonic tissues in mouse embryos[4] "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[3] "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[5] "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."

Notochord Development

Stage8 sem1.jpg Human Embryo notochordal plate

A scanning electron micrograph (SEM) image of the human embryo (Carnegie 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 | 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

Patterning

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


Development

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

Gray0065.jpg

Ossification endochondral 1c.jpg

Mouse Notochord

Mouse (E11) Notochord labeling HNF3beta[6]
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
PMID25343614}}

Abnormalities

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.[7]

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.[7]

Tornwaldt's cysts

A rare nasopharyngeal lesion occurring in humans thought to develop from remnants of the embryonic notochord adjacent with the embryonic foregut.[8][9]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.

Chordoma

Rare type of bone cancer arising from remnants of the embryonic notochord (for review see{{pmid:26363792|PMID26363792}}) Nearly all chordomas express the T-box transcription factor brachyury.


Links: Tbx | OMIM Chordoma | chordoma foundation


References

  1. 1.0 1.1 Ward L, Pang ASW, Evans SE & Stern CD. (2018). The role of the notochord in amniote vertebral column segmentation. Dev. Biol. , , . PMID: 29654746 DOI.
  2. 2.0 2.1 LLeras Forero L, Narayanan R, Huitema LFA, VanBergen M, Apschner A, Peterson-Maduro J, Logister I, Valentin G, Morelli LG, Oates A & Schulte-Merker S. (2018). Segmentation of the zebrafish axial skeleton relies on notochord sheath cells and not on the segmentation clock. Elife , 7, . PMID: 29624170 DOI.
  3. 3.0 3.1 Shapiro IM & Risbud MV. (2010). Transcriptional profiling of the nucleus pulposus: say yes to notochord. Arthritis Res. Ther. , 12, 117. PMID: 20497604 DOI.
  4. Imuta Y, Koyama H, Shi D, Eiraku M, Fujimori T & Sasaki H. (2014). Mechanical control of notochord morphogenesis by extra-embryonic tissues in mouse embryos. Mech. Dev. , 132, 44-58. PMID: 24509350 DOI.
  5. Bressan M, Davis P, Timmer J, Herzlinger D & Mikawa T. (2009). Notochord-derived BMP antagonists inhibit endothelial cell generation and network formation. Dev. Biol. , 326, 101-11. PMID: 19041859 DOI.
  6. Hajduk P, Sato H, Puri P & Murphy P. (2011). Abnormal notochord branching is associated with foregut malformations in the adriamycin treated mouse model. PLoS ONE , 6, e27635. PMID: 22132119 DOI.
  7. 7.0 7.1 Lagman C, Varshneya K, Sarmiento JM, Turtz AR & Chitale RV. (2016). Proposed Diagnostic Criteria, Classification Schema, and Review of Literature of Notochord-Derived Ecchordosis Physaliphora. Cureus , 8, e547. PMID: 27158576 DOI.
  8. Miyahara H & Matsunaga T. (1994). Tornwaldt's disease. Acta Otolaryngol Suppl , 517, 36-9. PMID: 7856446
  9. Moody MW, Chi DH, Chi DM, Mason JC, Phillips CD, Gross CW & Schlosser RJ. (2007). Tornwaldt's cyst: incidence and a case report. Ear Nose Throat J , 86, 45-7, 52. PMID: 17315835

Reviews

Lawson LY & Harfe BD. (2017). Developmental mechanisms of intervertebral disc and vertebral column formation. Wiley Interdiscip Rev Dev Biol , 6, . PMID: 28719048 DOI.

Risbud MV & Shapiro IM. (2011). Notochordal cells in the adult intervertebral disc: new perspective on an old question. Crit. Rev. Eukaryot. Gene Expr. , 21, 29-41. PMID: 21967331

Risbud MV, Schaer TP & Shapiro IM. (2010). Toward an understanding of the role of notochordal cells in the adult intervertebral disc: from discord to accord. Dev. Dyn. , 239, 2141-8. PMID: 20568241 DOI.

Stemple DL. (2005). Structure and function of the notochord: an essential organ for chordate development. Development , 132, 2503-12. PMID: 15890825 DOI.

Articles

Imuta Y, Koyama H, Shi D, Eiraku M, Fujimori T & Sasaki H. (2014). Mechanical control of notochord morphogenesis by extra-embryonic tissues in mouse embryos. Mech. Dev. , 132, 44-58. PMID: 24509350 DOI.

Korecki CL, Taboas JM, Tuan RS & Iatridis JC. (2010). Notochordal cell conditioned medium stimulates mesenchymal stem cell differentiation toward a young nucleus pulposus phenotype. Stem Cell Res Ther , 1, 18. PMID: 20565707 DOI.

Christiansen HE, Lang MR, Pace JM & Parichy DM. (2009). Critical early roles for col27a1a and col27a1b in zebrafish notochord morphogenesis, vertebral mineralization and post-embryonic axial growth. PLoS ONE , 4, e8481. PMID: 20041163 DOI.

Edeling MA, Sanker S, Shima T, Umasankar PK, Höning S, Kim HY, Davidson LA, Watkins SC, Tsang M, Owen DJ & Traub LM. (2009). Structural requirements for PACSIN/Syndapin operation during zebrafish embryonic notochord development. PLoS ONE , 4, e8150. PMID: 19997509 DOI.

Lee JD & Anderson KV. (2008). Morphogenesis of the node and notochord: the cellular basis for the establishment and maintenance of left-right asymmetry in the mouse. Dev. Dyn. , 237, 3464-76. PMID: 18629866 DOI.

Search PubMed

Search NLM Online Textbooks: "Notochord" : Developmental Biology | The Cell- A molecular Approach | Molecular Biology of the Cell | Endocrinology


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Cite this page: Hill, M.A. (2018, July 20) Embryology Notochord. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Notochord

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