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Cite this page: Hill, M.A. (2024, April 13) Embryology Notochord. Retrieved from

10 Most Recent Papers

Note - This sub-heading shows an automated computer PubMed search using the listed sub-heading term. References appear in this list based upon the date of the actual page viewing. Therefore the list of references do not reflect any editorial selection of material based on content or relevance. In comparison, references listed on the content page and discussion page (under the publication year sub-headings) do include editorial selection based upon relevance and availability. (More? Pubmed Most Recent)

Notochord Development

<pubmed limit=5>Notochord Development</pubmed>


The development of the human notochord

PLoS One. 2018 Oct 22;13(10):e0205752. doi: 10.1371/journal.pone.0205752. eCollection 2018.

de Bree K1, de Bakker BS1, Oostra RJ1. Author information Abstract The notochord is a major regulator of embryonic patterning in vertebrates and abnormal notochordal development is associated with a variety of birth defects in man. Proper knowledge of the development of the human notochord, therefore, is important to understand the pathogenesis of these birth defects. Textbook descriptions vary significantly and seem to be derived from both human and animal data whereas the lack of references hampers verification of the presented data. Therefore, a verifiable and comprehensive description of the development of the human notochord is needed. Our analysis and three-dimensional (3D) reconstructions of 27 sectioned human embryos ranging from Carnegie Stage 8 to 15 (17-41 days of development), resulted in a comprehensive and verifiable new model of notochordal development. Subsequent to gastrulation, a transient group of cells briefly persists as the notochordal process which is incorporated into the endodermal roof of the gut while its dorsal side attaches to the developing neural tube. Then, the notochordal process embeds entirely into the endoderm, forming the epithelial notochordal plate, which remains intimately associated with the neural tube. Subsequently, the notochordal cells detach from the endoderm to form the definitive notochord, allowing the paired dorsal aortae to fuse between the notochord and the gut. We show that the formation of the notochordal process and plate proceeds in cranio-caudal direction. Moreover, in contrast to descriptions in the modern textbooks, we report that the formation of the definitive notochord in humans starts in the middle of the embryo, and proceeds in both cranial and caudal directions. PMID: 30346967 DOI: 10.1371/journal.pone.0205752

Human Notochord Timeline
Carnegie Stage Days Event
7 15 to 17 notochordal process directly rostral to the area of gastrulation.
8 to 10 17 to 23 group of undifferentiated cells that briefly persists. Within the notochordal process, a connection between the amniotic cavity and yolk-sac (neurenteric canal).
8 to 11 17 to 26 notochordal process incorporates entirely into the endoderm, forming the epithelial notochordal plate.
10 to 11 21 to 26 notochordal plate then acquires an “inverted U-shape”, relatively lengthens during these stages and remains intimately associated with the neural tube until stage 12 (26–30 days).
12 26 to 30 notochordal plate detaches completely from the endoderm to form the definitive notochord.
12 to 14 26 to 35 definitive notochord formation then allows the paired dorsal aortae to fuse in-between the notochord and the roof of the gut.
Table data[1]   Links: notochord | timeline | Week 3 | Week 4

The role of the notochord in amniote vertebral column segmentation

Dev Biol. 2018 Apr 11. pii: S0012-1606(18)30022-8. doi: 10.1016/j.ydbio.2018.04.005. [Epub ahead of print]

Ward L1, Pang ASW1, Evans SE1, Stern CD2.


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. PMID: 29654746 DOI: 10.1016/j.ydbio.2018.04.005

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

Elife. 2018 Apr 6;7. pii: e33843. doi: 10.7554/eLife.33843. [Epub ahead of print]

LLeras Forero L1, Narayanan R2, Huitema LFA3, VanBergen M1, Apschner A3, Peterson-Maduro J3, Logister I3, Valentin G4, Morelli LG5, Oates A2, Schulte-Merker S1.

Abstract 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. KEYWORDS: developmental biology; stem cells; zebrafish PMID: 29624170 DOI: 10.7554/eLife.33843


The molecular aspects of chordoma

Neurosurg Rev. 2016 Apr;39(2):185-96; discussion 196. doi: 10.1007/s10143-015-0663-x. Epub 2015 Sep 12.

Gulluoglu S1,2, Turksoy O1, Kuskucu A2, Ture U3, Bayrak OF4.


Chordomas are one of the rarest bone tumors, and they originate from remnants of embryonic notochord along the spine, more frequently at the skull base and sacrum. Although they are relatively slow growing and low grade, chordomas are highly recurrent, aggressive, locally invasive, and prone to metastasize to the lungs, bone, and the liver. Chordomas highly and generally show a dual epithelial-mesenchymal differentiation. These tumors resist chemotherapy and radiotherapy; therefore, radical surgery and high-dose radiation are the most used treatments, although there is no standard way to treat the disease. The molecular biology process behind the initiation and progression of a chordoma needs to be revealed for a better understanding of the disease and to develop more effective therapies. Efforts to discover the mysteries of these molecular aspects have delineated several molecular and genetic alterations in this tumor. Here, we review and describe the emerging insights into the molecular landscape of chordomas.

KEYWORDS: Chordoma; Gene expression; Molecular pathology; Molecular pathways PMID 26363792

Proposed Diagnostic Criteria, Classification Schema, and Review of Literature of Notochord-Derived Ecchordosis Physaliphora

Cureus. 2016 Mar 30;8(3):e547. doi: 10.7759/cureus.547.

Lagman C1, Varshneya K2, Sarmiento JM3, Turtz AR1, Chitale RV4.


Ecchordosis physaliphora (EP) is a benign notochordal remnant derived from ectopic nests found along the craniospinal axis. It typically presents asymptomatically and is diagnosed using classic radiologic features, particularly location, T1-hypointensity, T2-hyperintensity, and lack of enhancement following gadolinium (Gd) contrast administration. Distinguishing EP from its malignant counterpart, chordoma, is of paramount importance, given the aggressive nature of the latter. Advances in imaging and immunohistochemistry have aided in diagnosis to an extent but, to our knowledge, identification of the genetic fingerprint of EP has yet to take place. Further cytological analysis of these lesions in search of a genetic link is warranted. We propose here a set of diagnostic criteria based on features consistently cited in the literature. In this literature review, 23 case reports were identified and collated into a summary of symptomatic cases of ecchordosis physaliphora. An illustrative case report of two patients was also included.

KEYWORDS: chordoma; ecchordosis physaliphora; notochordal remnant; retroclival lesion PMID 27158576


The notochord: structure and functions

Cell Mol Life Sci. 2015 Apr 2. [Epub ahead of print]

Corallo D1, Trapani V, Bonaldo P.


The notochord is an embryonic midline structure common to all members of the phylum Chordata, providing both mechanical and signaling cues to the developing embryo. In vertebrates, the notochord arises from the dorsal organizer and it is critical for proper vertebrate development. This evolutionary conserved structure located at the developing midline defines the primitive axis of embryos and represents the structural element essential for locomotion. Besides its primary structural function, the notochord is also a source of developmental signals that patterns surrounding tissues. Among the signals secreted by the notochord, Hedgehog proteins play key roles during embryogenesis. The Hedgehog signaling pathway is a central regulator of embryonic development, controlling the patterning and proliferation of a wide variety of organs. In this review, we summarize the current knowledge on notochord structure and functions, with a particular emphasis on the key developmental events that take place in vertebrates. Moreover, we discuss some genetic studies highlighting the phenotypic consequences of impaired notochord development, which enabled to understand the molecular basis of different human congenital defects and diseases.

PMID 25833128


FoxA4 favours notochord formation by inhibiting contiguous mesodermal fates and restricts anterior neural development in Xenopus embryos

PLoS One. 2014 Oct 24;9(10):e110559. doi: 10.1371/journal.pone.0110559. eCollection 2014.

Murgan S1, Castro Colabianchi AM1, Monti RJ1, Boyadjián López LE1, Aguirre CE1, Stivala EG1, Carrasco AE1, López SL1.


In vertebrates, the embryonic dorsal midline is a crucial signalling centre that patterns the surrounding tissues during development. Members of the FoxA subfamily of transcription factors are expressed in the structures that compose this centre. Foxa2 is essential for dorsal midline development in mammals, since knock-out mouse embryos lack a definitive node, notochord and floor plate. The related gene foxA4 is only present in amphibians. Expression begins in the blastula -chordin and -noggin expressing centre (BCNE) and is later restricted to the dorsal midline derivatives of the Spemann's organiser. It was suggested that the early functions of mammalian foxa2 are carried out by foxA4 in frogs, but functional experiments were needed to test this hypothesis. Here, we show that some important dorsal midline functions of mammalian foxa2 are exerted by foxA4 in Xenopus. We provide new evidence that the latter prevents the respecification of dorsal midline precursors towards contiguous fates, inhibiting prechordal and paraxial mesoderm development in favour of the notochord. In addition, we show that foxA4 is required for the correct regionalisation and maintenance of the central nervous system. FoxA4 participates in constraining the prospective rostral forebrain territory during neural specification and is necessary for the correct segregation of the most anterior ectodermal derivatives, such as the cement gland and the pituitary anlagen. Moreover, the early expression of foxA4 in the BCNE (which contains precursors of the whole forebrain and most of the midbrain and hindbrain) is directly required to restrict anterior neural development.

PMID 25343614

Mechanical control of notochord morphogenesis by extra-embryonic tissues in mouse embryos

Mech Dev. 2014 May;132:44-58. doi: 10.1016/j.mod.2014.01.004. Epub 2014 Feb 7.

Imuta Y1, Koyama H2, Shi D3, Eiraku M4, Fujimori T2, Sasaki H5.


Mammalian embryos develop in coordination with extraembryonic tissues, which support embryonic development by implanting embryos into the uterus, supplying nutrition, providing a confined niche, and also providing patterning signals to embryos. 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. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved. KEYWORDS: Amniotic cavity; Convergent extension; Live imaging; Mechanical forces; Mouse embryogenesis; Notochord

PMID 24509350


Zinc finger protein 219-like (ZNF219L) and Sox9a regulate synuclein-γ2 (sncgb) expression in the developing notochord of zebrafish

Biochem Biophys Res Commun. 2013 Dec 13;442(3-4):189-94. doi: 10.1016/j.bbrc.2013.11.042. Epub 2013 Nov 20.

Lien HW, Yang CH, Cheng CH, Liao YF, Han YS, Huang CJ. Source Institute of Fisheries Sciences, National Taiwan University, Taipei 106, Taiwan.

Abstract Zebrafish synuclein-γ2 (sncgb) has been reported to be expressed specifically in the notochord. However, the mechanism by which the sncgb gene promoter is regulated has not been described. In this paper, we demonstrate that Zinc finger protein 219-like (ZNF219L) and sox9a are involved in the regulation of sncgb gene expression. Furthermore, we observed that over-expression of both ZNF219L and Sox9a resulted in increased sncgb expression. In addition, ZNF219L is physically associated with Sox9a, and simultaneous morpholino knockdown of znf219L and sox9a caused a synergistic decrease of sncgb expression in the notochord. Taken together, our results reveal that coordination of ZNF219L with Sox9a is involved in the regulation of notochord-specific expression of sncgb. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved. KEYWORDS: Notochord, Sox9a, Synuclein-γ2 (sncgb), ZNF219-like (ZNF219L), Zebrafish

PMID 24269816

Foxa1 and foxa2 are required for formation of the intervertebral discs

PLoS One. 2013;8(1):e55528. doi: 10.1371/journal.pone.0055528. Epub 2013 Jan 31.

Maier JA, Lo Y, Harfe BD. Source Molecular Genetics and Microbiology and the Genetics Institute, University of Florida, College of Medicine, Gainesville, Florida, United States of America.


The intervertebral disc (IVD) is composed of 3 main structures, the collagenous annulus fibrosus (AF), which surrounds the gel-like nucleus pulposus (NP), and hyaline cartilage endplates, which are attached to the vertebral bodies. An IVD is located between each vertebral body. Degeneration of the IVD is thought to be a major cause of back pain, a potentially chronic condition for which there exist few effective treatments. The NP forms from the embryonic notochord. Foxa1 and Foxa2, transcription factors in the forkhead box family, are expressed early during notochord development. However, embryonic lethality and the absence of the notochord in Foxa2 null mice have precluded the study of potential roles these genes may play during IVD formation. Using a conditional Foxa2 allele in conjunction with a tamoxifen-inducible Cre allele (ShhcreER(T2)), we removed Foxa2 from the notochord of E7.5 mice null for Foxa1. Foxa1(-/-);Foxa2(c/c);ShhcreER(T2) double mutant animals had a severely deformed nucleus pulposus, an increase in cell death in the tail, decreased hedgehog signaling, defects in the notochord sheath, and aberrant dorsal-ventral patterning of the neural tube. Embryos lacking only Foxa1 or Foxa2 from the notochord were indistinguishable from control animals, demonstrating a functional redundancy for these genes in IVD formation. In addition, we provide in vivo genetic evidence that Foxa genes are required for activation of Shh in the notochord.

PMID 23383217

Notochord vacuoles are lysosome-related organelles that function in axis and spine morphogenesis

J Cell Biol. 2013 Mar 4;200(5):667-79. doi: 10.1083/jcb.201212095.

Ellis K, Bagwell J, Bagnat M. Author information


The notochord plays critical structural and signaling roles during vertebrate development. At the center of the vertebrate notochord is a large fluid-filled organelle, the notochord vacuole. Although these highly conserved intracellular structures have been described for decades, little is known about the molecular mechanisms involved in their biogenesis and maintenance. Here we show that zebrafish notochord vacuoles are specialized lysosome-related organelles whose formation and maintenance requires late endosomal trafficking regulated by the vacuole-specific Rab32a and H(+)-ATPase-dependent acidification. We establish that notochord vacuoles are required for body axis elongation during embryonic development and identify a novel role in spine morphogenesis. Thus, the vertebrate notochord plays important structural roles beyond early development.

PMID 23460678



Ecchordosis physaliphora - a case report and a review of notochord-derived lesions

Neurol Neurochir Pol. 2011 Mar-Apr;45(2):169-73.

Adamek D, Malec M, Grabska N, Krygowska-Wajs A, Gałązka K. Source Department of Pathology, Jagiellonian University Medical College, Krakow.


Some notochord cells remain along the axis of the vertebral column after embryogenesis. These 'notochordal remnants' have some similarities, but their biological behaviour varies considerably. They can give rise to benign lesions such as ecchordosis physaliphora (EP) and 'benign notochordal cell tumour' (BNCT), or aggressive ones like chordoma. We review the problems of the differential diagnosis of notochordal remnants apropos of a case of the incidental autopsy finding of EP in a 78-year-old man, who died due to heart infarction. The 6-mm asymptomatic gelatinous lesion was fixed to the basilar artery on its ventral aspect. Small EPs can be easily overlooked in autopsy. Ecchordosis physaliphora and intradural chordoma share some similarities that may be misleading and may even result in the wrong diagnosis and therapy. The recently reported new entity BNCT poses a similar problem. We review the literature illustrating the most important features of notochord-derived lesions and discuss the relationships between these lesions with regard to molecular genetics.

PMID 21574122

Notochordal cells in the adult intervertebral disc: new perspective on an old question

Crit Rev Eukaryot Gene Expr. 2011;21(1):29-41.

Risbud MV, Shapiro IM. Source Department of Orthopaedic Surgery and Graduate Program in Tissue Engineering and Regenerative Medicine, Thomas Jefferson University, Philadelphia, PA, USA.


The intervertebral disc is a tissue positioned between each of the vertebrae that accommodates applied biomechanical forces to the spine. The central compartment of the disc contains the nucleus pulposus (NP) which is enclosed by the annulus fibrosus and the endplate cartilage.The NP is derived from the notochord, a rod-like structure of mesodermal origin. Development of the notochord is tightly regulated by interactive transcription factors and target genes. Since a number of these molecules are unique they have be used for cell lineage and fate mapping studies of tissues of the intervertebral disc. These studies have shown that in a number of species including human, NP tissue retains notochordal cells throughout life. In the adult NP, there are present both large and small notochordal cells, as well as a progenitor cell population which can differentiate along the mesengenic pathway. Since tissue renewal in the intervertebral disc is dependent on the ability of these cells to commit to the NP lineage and undergo terminal differentiation, studies have been performed to assess which signaling pathways may regulate these activities. The notch signaling pathway is active in the intervertebral disc and is responsive to hypoxia, probably through HIF-1a. From a disease viewpoint, it is hypothesized that an oxemic shift, possibly mediated by alterations in the vascular supply to the tissues of the disc would be expected to lead to a failure in notochordal progenitor cell activation and a decrease in the number of differentiated cells. In turn, this would lead to decrements in function and enhancement of the effect of agents that are known to promote disc degeneration.

PMID 21967331


T (brachyury) gene duplication confers major susceptibility to familial chordoma.

Nat Genet. 2009 Nov;41(11):1176-8. Epub 2009 Oct 4.

Yang XR, Ng D, Alcorta DA, Liebsch NJ, Sheridan E, Li S, Goldstein AM, Parry DM, Kelley MJ.

Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. Abstract Using high-resolution array-CGH, we identified unique duplications of a region on 6q27 in four multiplex families with at least three cases of chordoma, a cancer of presumed notochordal origin. The duplicated region contains only the T (brachyury) gene, which is important in notochord development and is expressed in most sporadic chordomas. Our findings highlight the value of screening for complex genomic rearrangements in searches for cancer-susceptibility genes.

PMID 19801981


Relationship between notochord and the bursa pharyngea in early human development

Cell Differ Dev. 1990 Dec 1;32(2):125-30.

Babić MS. Source Institute of Histology and Embryólogy, Faculty of Medicine, University of Zagreb, Yugoslavia. Abstract The spatial relationship of the notochord to the pharyngeal endoderm of 5- to 12-week human embryos was investigated. The light microscopic observations showed a close association of the notochord and endoderm during the 5th embryonic week. Later on, interposition of the mesenchymal cells caused a progressive separation of these two structures. They remained in close apposition only in the area of bursa pharyngea, a deep invagination of the dorsal pharyngeal epithelium. Ultrastructural examination of a 5-week-old embryo revealed cell processes between the juxtaposed notochordal and endodermal cells in the region of the future bursa pharyngea. In already separated areas, mesenchymal cells, well developed basal laminae and small amounts of extracellular matrix were observed in the notochord-endoderm interspace. The observations revealed a sequence of basal lamina formation during notochord-endoderm separation. The stage-dependent lack of basal lamina at the site of the future bursa pharyngea could reflect direct local interactions between notochordal and endodermal cells.

PMID 2083396


Notochordal-basichondrocranium relationships: abnormalities in experimental axial skeletal (dysraphic) disorders

J Embryol Exp Morphol. 1979 Oct;53:15-38.

Marin-Padilla M. (By Miguel Marin-Padilla Professor of Pathology, Dartmouth Medical School)

PMID 536685

"The human notochord on emerging from the vertebral axis through the odontoid process of the second vertebra, bends slightly and forms a distinct enlargement dorsal and posterior to the base of the skull. It then enters and crosses diagonally the posterior region of the basioccipital, where it forms two noticeable enlargements (Fig. \A, arrow). On leaving the basioccipital ventrally, it establishes one or more contacts with the pharyngeal epithelium (Fig. 1B). It then continues cephalad under the basioccipital and turns dorsally, penetrating and terminating within the basisphenoid near the region of the hypophysis (Fig. 1^4). The notochord terminates in a few short branches.

In essence, this description coincides with and confirms the intracranial course of the human notochord described by early investigators (Gage, 1906; Bardeen, 1908; Fawcett, 1910; Huber, 1912; Macklin, 1914). However, Williams (1908) depicts the human notochord within the basal plate in its entirety without recognizable contacts with the pharyngeal epithelium. This particular intracranial course of the notochord could represent a normal variation, according to some investigators (Froriep, 1882; Killian, 1888; Huber, 1912; Snook, 1934), who pointed out that pharyngeal contacts are present in about 50 % of the embryos studied.

The distinct contact between the human notochord and the epithelium of the bursa pharyngea illustrated in this study (Fig. 1B) has also been described by early (Froriep, 1882; Killian, 1888; Gage, 1906; Huber, 1912) as well as by recent (Snook, 1934; Slipka, 1972) investigators. The bursa pharyngea appears to be a peculiar human developmental structure seldom described in other mammals (Tourneux, 1912). Practically nothing is known about the significance or function of this structure of which only a mere mention can be found in leading books on human embryology.

In the human embryos, as well as in the hamster embryos studied (see later), the notochord penetrates the posterior region of the basioccipital, where it forms noticeable focal enlargements (Figs. 1, 2, 5, 7, 10) which are similar to those described by Slipka (1974) in pig embryos. I fully agree with Slipka's interpretation concerning the segmental nature of these occipital notochordal enlargements. He considers them to be homologous to the notochordal en- largements formed between the anlage of the developing vertebrae. The occipital bone (basioccipital, lateral occipital, and the planum nuchale of the squama) develops, as do the vertebrae, from three pairs of somites which constitute rudimentary occipital vertebrae (De Beer, 1937; Hamilton, Boyd & Mossman, 1972). The two occipital notochordal enlargements described in human, hamster and pig embryos could represent the intermediate segments between the three rudimentary occipital vertebrae. The notochordal enlargement formed between the vertebral column and the basioccipital, which is recognizable in most of the embryos studied herein, could well represent the third segment. The segmented (somitic) nature of the occipital bone disappears early in development when its various elements fuse together to form a single structure which then becomes incorporated into the base of the skull. The presence of more than one hypoglossal nerve canal in the lateral occipitals is considered to be an indication of the segmental origin of this bone (De Beer, 1937). Furthermore, in some pathological conditions known to affect the vertebrae specifically, such as some chondrodystrophies, the occipital bone is also affected, behaving in these cases more as a vertebra than as a component of the base of the skull (Marin-Padilla & Marin-Padilla, 1977)."

  1. de Bree K, de Bakker BS & Oostra RJ. (2018). The development of the human notochord. PLoS ONE , 13, e0205752. PMID: 30346967 DOI.