Musculoskeletal System - Axial Skeleton Development

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Introduction

Adult axial skeleton

During the 3rd week the paraxial mesoderm forms into "balls" of mesoderm paired either side of the neural groove, called somites. Different regions of the somite differentiate into dermomyotome (dermal and muscle component) and sclerotome (forms vertebral column). Vertebral bone is formed through a lengthy process involving endochondrial ossification of a cartilage formed from mesenchyme.

The vertebral body begins as a bony collar that expands into regions of dying cartilage. The bony vertebral arch, enclosing the spinal cord, forms later and the arch remains open dorsally (linked by a ligament) to allow growth of the spinal cord.

The axial skeleton consists of: Skull, Auditory Ossicles, Hyoid bone, Vertebral column, Chest (sternum, ribs)

The vertebral column is a series of bone segments (vertebra) separated by specialized joints (intervertebral disc).

In the adult, the vertebra form rostro-caudally: 7 cervical, 12 thoracic, 5 lumbar, 1 sacrum, coccyx. There has been identified a population variability in the final number of vertebra.

Skeletal ossification continues postnatally, through puberty until mid 20s. Abnormalities of vertebral column development can lead to defects including scoliosis.


Musculoskeletal Links: Introduction | Mesoderm | Somitogenesis | Limb | Cartilage | Bone | Bone Timeline | Axial Skeleton | Skull | Joint | Muscle | Tendon | Diaphragm | Lecture - Musculoskeletal Development | Abnormalities | Limb Abnormalities | Cartilage Histology | Bone Histology | Skeletal Muscle Histology | Category:Musculoskeletal
Historic Embryology: 1910 Vertebral Column

Some Recent Findings

  • Ossification of the vertebral column in human foetuses: histological and computed tomography studies[1] "There is no agreement in the literature as to the time of the onset and progress of the vertebral column ossification. The aim of the present study was to determine the precise sequence of ossification of the neural arches and vertebral centra.Histological and radiographic studies were performed on 27 human foetuses aged from 9 to 21 weeks. It was found that the ossification of vertebrae commences in foetuses aged 10 and 11 weeks. Ossification centres appear first for neuralarches in the cervical and upper thoracic vertebrae and by the end of 11th week they are present in all thoracic and lumbar neural arches. In the vertebral centrain foetus of 10 weeks ossification was found in the lower 7 thoracic and first lumbar vertebrae. By the end of 11th week ossification is present in the lower 4 cervical, all thoracic, all lumbar and 4 sacral vertebral centra."
  • Foxa1 and foxa2 are required for formation of the intervertebral discs[2] "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. ... The NP forms from the embryonic notochord. Foxa1 and Foxa2, transcription factors in the forkhead box family, are expressed early during notochord development. ...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."
  • Role of environmental factors in axial skeletal dysmorphogenesis[3] "Approximately 1 in 1000 live births is afflicted with an axial skeletal defect. Although many of the known human teratogens can produce axial skeletal defects, the etiology of over half of the observed defects is unknown."
  • Embryology and bony malformations of the craniovertebral junction.[4] "The embryology of the bony craniovertebral junction (CVJ) is reviewed with the purpose of explaining the genesis and unusual configurations of the numerous congenital malformations in this region. ...A logical classification of this seemingly unwieldy group of malformations is thus possible based on their ontogenetic lineage, morbid anatomy, and clinical relevance. Representative examples of the main constituents of this classification scheme are given, and their surgical treatments are selectively discussed."
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


Search term: Axial Skeleton Development

Maiko Matsui, John Klingensmith Multiple tissue-specific requirements for the BMP antagonist noggin in development of the mammalian craniofacial skeleton. Dev. Biol.: 2014; PMID:24949938 Sarah Beck-Cormier, Marie Escande, Céline Souilhol, Sandrine Vandormael-Pournin, Sophie Sourice, Paul Pilet, Charles Babinet, Michel Cohen-Tannoudji Notchless is required for axial skeleton formation in mice. PLoS ONE: 2014, 9(5);e98507 PMID:24875805 C Chase Bolt, Colleen M Elso, Xiaochen Lu, Fuming Pan, Andreas Kispert, Lisa Stubbs A distant downstream enhancer directs essential expression of Tbx18 in urogenital tissues. Dev. Biol.: 2014; PMID:24854998 Denis Poddubnyy, Joachim Sieper Similarities and differences between nonradiographic and radiographic axial spondyloarthritis: a clinical, epidemiological and therapeutic assessment. Curr Opin Rheumatol: 2014; PMID:24807404 Kai Dittmann, Manuela Wuelling, Anja Uhmann, Christian Dullin, Heidi Hahn, Stefan Schweyer, Andrea Vortkamp, Jürgen Wienands Inactivation of patched1 in murine chondrocytes causes spinal fusion without inflammation. Arthritis Rheumatol: 2014, 66(4);831-40 PMID:24757136

Textbooks

Developing vertebra
  • The Developing Human: Clinically Oriented Embryology (8th Edition) by Keith L. Moore and T.V.N Persaud - Moore & Persaud Chapter 15 the skeletal system
  • Larsen’s Human Embryology by GC. Schoenwolf, SB. Bleyl, PR. Brauer and PH. Francis-West - Chapter 11 Limb Dev (bone not well covered in this textbook)
  • Before we Are Born (5th ed.) Moore and Persaud Chapter 16,17: p379-397, 399-405
  • Essentials of Human Embryology Larson Chapter 11 p207-228

Objectives

  • Identify the components of a somite and the adult derivatives of each component.
  • Give examples of sites of (a) endochondral and (b) intramembranous ossification and to compare these two processes.
  • Identify the general times (a) of formation of primary and (b) of formation of secondary ossification centres, and (c) of fusion of such centres with each other.
  • Briefly summarise the development of the limbs.
  • Describe the developmental abnormalities responsible for the following malformations: selected growth plate disorders; congenital dislocation of the hip; scoliosis; arthrogryposis; and limb reduction deformities.

Development Overview

Below is a very brief overview using simple figures of 3 aspects of early musculoskeletal development. More detailed overviews are shown on other notes pages Mesoderm and Somite, Vertebral Column, Limb in combination with serial sections and Carnegie images.

Mesoderm Development

Mesoderm cartoon 01.jpg Cells migrate through the primitive streak to form mesodermal layer. Extraembryonic mesoderm lies adjacent to the trilaminar embryo totally enclosing the amnion, yolk sac and forming the connecting stalk.
Mesoderm cartoon 02.jpg Paraxial mesoderm accumulates under the neural plate with thinner mesoderm laterally. This forms 2 thickened streaks running the length of the embryonic disc along the rostrocaudal axis. In humans, during the 3rd week, this mesoderm begins to segment. The neural plate folds to form a neural groove and folds.
Mesoderm cartoon 03.jpg Segmentation of the paraxial mesoderm into somites continues caudally at 1 somite/90minutes and a cavity (intraembryonic coelom) forms in the lateral plate mesoderm separating somatic and splanchnic mesoderm.

Note intraembryonic coelomic cavity communicates with extraembryonic coelom through portals (holes) initially on lateral margin of embryonic disc.

Mesoderm cartoon 04.jpg Somites continue to form. The neural groove fuses dorsally to form a tube at the level of the 4th somite and "zips up cranially and caudally and the neural crest migrates into the mesoderm.

Somite Development

Mesoderm cartoon 05.jpg Mesoderm beside the notochord (axial mesoderm, blue) thickens, forming the paraxial mesoderm as a pair of strips along the rostro-caudal axis.
Mesoderm cartoon 06.jpg Paraxial mesoderm towards the rostral end, begins to segment forming the first somite. Somites are then sequentially added caudally. The somitocoel, is a cavity forming in early somites, which is lost as the somite matures.
Mesoderm cartoon 07.jpg Cells in the somite differentiate medially to form the sclerotome (forms vertebral column) and dorsolaterally to form the dermomyotome.
Mesoderm cartoon 08.jpg The dermomyotome then forms the dermotome (forms dermis) and myotome (forms muscle).

Neural crest cells migrate beside and through somite.

Mesoderm cartoon 09.jpg The myotome differentiates to form 2 components dorsally the epimere and ventrally the hypomere, which in turn form epaxial and hypaxial muscles respectively. The bulk of the trunk and limb muscle coming from the Hypaxial mesoderm. Different structures will be contributed depending upon the somite level.

Axial Features

  • human occipitocervical segmentation[5]
  • head and vertebral column boundary - located between the 5th and 6th somites[6]
  • craniovertebral junction - caudal occiput, atlas, and axis[7]

Embryonic Development

Week 8

Stage22 vertebra and spinal cord 1.jpg

Human embryo (Stage 22) vertebra and spinal cord development. Note the structure of the vertebral arch, the dorsal ligament allowing expansion of the arch to accommodate spinal cord growth.

Skull

Skull anterior.gif

See Skull Development

Links: Skull Development

Vertebral Column

Cervical Vertebra

Vertebral element ossification between species.[8]
  • C1 - (atlas) from fourth occipital and first cervical sclerotomes. Posterior arch ossifies from 2 centres in the lateral masses fusing postnatally between 3 - 5th years.

A comparison of vertebral element ossification between different species also in relation to Hox gene expression.[8]

  • For each taxon, circles indicate centra, and squares indicate left and right neural arches.
  • Colours represent the order of ossification.
  • Hox expression boundaries in the mouse (placentals) and vertebral segment identity are shown at right.
  • Conserved timing of V7 centrum ossification across mammals, including sloths (bradypus)
  • Overlap in Hox5-6 expression in the V6–V9 region of the sloth neck.


bradypus - three-toed sloths are the only members of this genus

dasypus - armadillo genus in the Dasypodidae family

Sacrum

Evolution of the sacrum[9] "In order to study the formation of the sacrum during the primate evolution, a new way of numbering mammalian vertebrae is presented; this demonstrates that the thoracolumbosacral complex is fixed at 22 vertebrae in 80% and at 22 +/- 1 in 100% of the cases. The shift of a vertebra from one type to another occurs either at the thoracolumbar or at the lumbosacral junction and not at the cervicothoracic junction. Rarely does the shift take place at the sacrococcygeal junction. Data from 318 primates reveal that the seven original lumbar vertebrae of the Old World monkeys are reduced in the great apes by a caudad "thoracization" of one to two lumbar vertebrae and a cephalad sacralization of one to four lumbar vertebrae. In the apes, sacralization is not total and different stages that are intermediate between lumbar and sacral are described. In Homo sapiens there is a total sacralization of the last two original lumbar vertebrae. In addition, development of the sacral wings (alae) is minimal in apes and reaches its maximum in hominids. The tendency of the hominoid sacrum to incorporate the last lumbar vertebrae and to widen markedly provides for an enhanced articulation of the sacrum with the ilium and offers a firm base of support for the trunk during erect posture. This is necessary for the support of the weight of the trunk above the sacrum and for the stabilization of the body during bipedal posture and locomotion. Encephalization did not play any major role in the widening of the sacrum since the former by far preceded the latter."

Intervertebral Disc

Mouse intervertebral disc (IVD) expression of transcription factor Nfatc1[10]

The adult intervertebral disc (IVD) has to bear the same loads as the vertebra and also have flexibility to allow axial column movement. This is achieved by a complex structure (cartilaginous end-plate) that links the vertebra above and below the disc to a outer dense fibrous structure (annulus fibrosus) containing a gel-like core region (nucleus pulposus). Some research in this area focusses on the degeneration of the IVD with ageing.

  • cartilaginous end-plate - that anchor the discs to the adjacent vertebral body bones
  • annulus fibrosus - cells are derived from the sclerotome
  • nucleus pulposus - cells are derived from the notochord[11]

Annulus Fibrosus

  • cells are derived from the sclerotome

Nucleus Pulposus

  • cells are derived from the notochord[11]
  • notochordal marker brachyury
  • proteoglycan rich extracellular matrix

Rib Development

Mouse E12.5 Sox9 Expression.jpg

Sox9 expression in the Mouse (E12.5) rib primordial.[12]


Molecular

Like many other embryonic structures there are two separate considerations:

  1. Pattern Formation - sclerotome differentiation and segmentation
  2. Overt Differentiation - mesoderm differentiation to cartilage differentiation and ossification to bone.

Notch

Links: Notch

Nuclear factor of activated T-cells, cytoplasmic 1

Mouse intervertebral disc (IVD) expression of transcription factor Nfatc1[10]
  • Transcription factor (Nfatc1) has been identified in developing mouse intervertebral disc (IVD).
  • The NFAT family of transcription factors regulates cytokine gene expression by binding to the promoter/enhancer regions of antigen-responsive genes, usually in cooperation with heterologous DNA-binding partners.
  • The activation of NFAT proteins is controlled by calcineurin, the calmodulin-dependent phosphatase.
Links: OMIM - NFATC1


Transforming growth factor beta

Two functions in IVD development:[10]

  1. prevent chondrocyte differentiation in the presumptive IVD
  2. promote differentiation of annulus fibrosus from sclerotome

Abnormalities

Spina Bifida

USA spina bifida rates.

Folic Acid and Neural Tube Defects

Absent Cervical Spine Pedicle

Absent cervical spine pedicle.jpg

Absent cervical spine pedicle[13]

The vertebral pedicles (Latin, pediculus ="small foot") are paired processes that project dorsally and connect the body of the spinal vertebra to the arch. Absence is a rare abnormality characterized by the absence of a pedicle of the affected vertebral body, seen most frequently at the level C6 followed by the level C5 and C7.

Scoliosis

Historic image scoliosis (Braune 1877)
Scoliometry[14]
Chêneau Brace[15]

International Classification of Diseases

Q67 Congenital musculoskeletal deformities of head, face, spine and chest - Q67.5 Congenital deformity of spine Congenital scoliosis: NOS postural Excl.: infantile idiopathic scoliosis (M41.0) scoliosis due to congenital bony malformation (Q76.3)


Scoliosis.jpg Scoliosis xray.jpg

  • frequency of congenital scoliosis is approximately 0.5, or 1 in 1,000 births.
  • assymetric growth impairment of vertebral bodies
  • lateral deviation of spine (Lateral flexion, Forward flexion, Rotation of vertebral column on long axis)
  • compensated by movement of vertebral column above and below affected region (producing a primary and two secondary curves)
  • progresses rapidly in adolescence and becomes fixed once bone growth is completed.
  • both genetic and environmental terartogens implicated.
    • a large number of chromosomal deletions relating to regions 2p13 – 15, 6q13 and 15q12 have been identified.


Links: Musculoskeletal System - Abnormalities

References

  1. A Skórzewska, M Grzymisławska, M Bruska, J Lupicka, W Woźniak Ossification of the vertebral column in human foetuses: histological and computed tomography studies. Folia Morphol. (Warsz): 2013, 72(3);230-8 PMID:24068685
  2. Jennifer A Maier, Yinting Lo, Brian D Harfe Foxa1 and foxa2 are required for formation of the intervertebral discs. PLoS ONE: 2013, 8(1);e55528 PMID:23383217 | PLOS One.
  3. Peter G Alexander, Rocky S Tuan Role of environmental factors in axial skeletal dysmorphogenesis. Birth Defects Res. C Embryo Today: 2010, 90(2);118-32 PMID:20544699
  4. Dachling Pang, Dominic N P Thompson Embryology and bony malformations of the craniovertebral junction. Childs Nerv Syst: 2011, 27(4);523-64 PMID:21193993 | PMC3055990 | {http://www.springerlink.com/content/yjn47x15520jn728/fulltext.html Childs Nerv Syst.]
  5. Fabiola Müller, Ronan O'Rahilly Segmentation in staged human embryos: the occipitocervical region revisited. J. Anat.: 2003, 203(3);297-315 PMID:14529047
  6. B Christ, J Wilting From somites to vertebral column. Ann. Anat.: 1992, 174(1);23-32 PMID:1605355
  7. Charles Raybaud Anatomy and development of the craniovertebral junction. Neurol. Sci.: 2011, 32 Suppl 3;267-70 PMID:21822704
  8. 8.0 8.1 Lionel Hautier, Vera Weisbecker, Marcelo R Sánchez-Villagra, Anjali Goswami, Robert J Asher Skeletal development in sloths and the evolution of mammalian vertebral patterning. Proc. Natl. Acad. Sci. U.S.A.: 2010, 107(44);18903-8 PMID:20956304 | Proc Natl Acad Sci U S A.
  9. M M Abitbol Evolution of the sacrum in hominoids. Am. J. Phys. Anthropol.: 1987, 74(1);65-81 PMID:3688211
  10. 10.0 10.1 10.2 Philip Sohn, Megan Cox, Dongquan Chen, Rosa Serra Molecular profiling of the developing mouse axial skeleton: a role for Tgfbr2 in the development of the intervertebral disc. BMC Dev. Biol.: 2010, 10;29 PMID:20214815 | PMC2848151 | BMC Dev Biol.
  11. 11.0 11.1 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 PMID:20568241
  12. Nicholas W Plummer, Karsten Spicher, Jason Malphurs, Haruhiko Akiyama, Joel Abramowitz, Bernd Nürnberg, Lutz Birnbaumer Development of the mammalian axial skeleton requires signaling through the Gα(i) subfamily of heterotrimeric G proteins. Proc. Natl. Acad. Sci. U.S.A.: 2012, 109(52);21366-71 PMID:23236180 | PMC3535641 | PNAS
  13. Roman Guggenberger, Gustav Andreisek, Hans Scheffel, Simon Wildermuth, Sebastian Leschka, Paul Stolzmann Absent cervical spine pedicle and associated congenital spinal abnormalities - a diagnostic trap in a setting of acute trauma: case report. BMC Med Imaging: 2010, 10;25 PMID:21062465 | BMC Med Imaging.
  14. Sietke G Postema, Corry K van der Sluis, Kristina Waldenlöv, Liselotte M Norling Hermansson Body structures and physical complaints in upper limb reduction deficiency: a 24-year follow-up study. PLoS ONE: 2012, 7(11);e49727 PMID:23226218 | PLoS One.
  15. Katarzyna Zaborowska-Sapeta, Ireneusz M Kowalski, Tomasz Kotwicki, Halina Protasiewicz-Fałdowska, Wojciech Kiebzak Effectiveness of Chêneau brace treatment for idiopathic scoliosis: prospective study in 79 patients followed to skeletal maturity. Scoliosis: 2011, 6(1);2 PMID:21266084 | PMC3037926 | Scoliosis


Reviews

Dachling Pang, Dominic N P Thompson Embryology and bony malformations of the craniovertebral junction. Childs Nerv Syst: 2011, 27(4);523-64 PMID:21193993

Tadahiro Iimura, Nicolas Denans, Olivier Pourquié Establishment of Hox vertebral identities in the embryonic spine precursors. Curr. Top. Dev. Biol.: 2009, 88;201-34 PMID:19651306

Tara Alexander, Christof Nolte, Robb Krumlauf Hox genes and segmentation of the hindbrain and axial skeleton. Annu. Rev. Cell Dev. Biol.: 2009, 25;431-56 PMID:19575673

Moisés Mallo, Tânia Vinagre, Marta Carapuço The road to the vertebral formula. Int. J. Dev. Biol.: 2009, 53(8-10);1469-81 PMID:19247958

Rochelle W Tyl, Neil Chernoff, John M Rogers Altered axial skeletal development. Birth Defects Res. B Dev. Reprod. Toxicol.: 2007, 80(6);451-72 PMID:18157900


Articles

Timothy J Mead, Katherine E Yutzey Notch pathway regulation of chondrocyte differentiation and proliferation during appendicular and axial skeleton development. Proc. Natl. Acad. Sci. U.S.A.: 2009, 106(34);14420-5 PMID:19590010

Susan Skuntz, Baljinder Mankoo, Minh-Thanh T Nguyen, Elisabeth Hustert, Atsuo Nakayama, Elisabeth Tournier-Lasserve, Christopher V E Wright, Vassilis Pachnis, Kapil Bharti, Heinz Arnheiter Lack of the mesodermal homeodomain protein MEOX1 disrupts sclerotome polarity and leads to a remodeling of the cranio-cervical joints of the axial skeleton. Dev. Biol.: 2009, 332(2);383-95 PMID:19520072

Valerie Wilson, Isabel Olivera-Martinez, Kate G Storey Stem cells, signals and vertebrate body axis extension. Development: 2009, 136(10);1591-604 PMID:19395637

Search PubMed

Search Pubmed: Axial Skeleton Development | Vertebra Development | Intervertebral Disc Development | Axial Skeleton Abnormalities

Additional Images

Terms

  • centrum - (vertebral body) anatomical term referring to the main bony part of the vertebra that forms the majority of the axial skeleton.
  • haemal arch - referring to the bony arch region within animal tail vertebra that contains blood vessels.
  • idiopathic scoliosis - clinical term for a spinal column deformity appearing usually postnatally after the age of 10 years old.
  • lordosis - clinical and anatomy term describing the curvature of the spine with the convexity toward the front. Normal to have lordosis in the cervical and lumbar regions of the spinal column.
  • neural arch - referring to the bony arch region within vertebra that contains the spinal cord.
  • notochord sheath - region surrounding the notochord. in teleost fish direct mineralization of this region, by intramembranous ossification, forms the initial vertebral centrum. (More? Zebrafish Development)
  • rib hump - clinical term for the prominence formed by ribs on the convexity of a curve, caused by rotation of the spine and attached ribs.
  • spinal column - term referring to the musculoskeletal elements (vertebrae, ligaments, and intervertebral discs), that surround the spinal cord and form the axial skeleton.
  • synsacrum - in birds sacral and lumbar vertebrae fused region forming elongated sacral region.


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Cite this page: Hill, M.A. (2014) Embryology Musculoskeletal System - Axial Skeleton Development. Retrieved July 4, 2014, from //embryology.med.unsw.edu.au/embryology/index.php?title=Musculoskeletal_System_-_Axial_Skeleton_Development

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Dr Mark Hill 2014, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G