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 | bone marrow | shoulder | pelvis | axial skeleton | skull | joint | skeletal muscle | muscle timeline | tendon | diaphragm | Lecture - Musculoskeletal | Lecture Movie | musculoskeletal abnormalities | limb abnormalities | developmental hip dysplasia | cartilage histology | bone histology | Skeletal Muscle Histology | Category:Musculoskeletal
Historic Embryology - Musculoskeletal  
1853 Bone | 1885 Sphenoid | 1902 - Pubo-femoral Region | Spinal Column and Back | Body Segmentation | Cranium | Body Wall, Ribs, and Sternum | Limbs | 1901 - Limbs | 1902 - Arm Development | 1906 Human Embryo Ossification | 1906 Lower limb Nerves and Muscle | 1907 - Muscular System | Skeleton and Limbs | 1908 Vertebra | 1908 Cervical Vertebra | 1909 Mandible | 1910 - Skeleton and Connective Tissues | Muscular System | Coelom and Diaphragm | 1913 Clavicle | 1920 Clavicle | 1921 - External body form | Connective tissues and skeletal | Muscular | Diaphragm | 1929 Rat Somite | 1932 Pelvis | 1940 Synovial Joints | 1943 Human Embryonic, Fetal and Circumnatal Skeleton | 1947 Joints | 1949 Cartilage and Bone | 1957 Chondrification Hands and Feet | 1968 Knee
Historic Embryology: 1910 Vertebral Column

Some Recent Findings

  • Role of environmental factors in axial skeletal dysmorphogenesis[1] "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.[2] "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."

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[3]
  • head and vertebral column boundary - located between the 5th and 6th somites[4]
  • craniovertebral junction - caudal occiput, atlas, and axis[5]

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

Vertebral Column

Cervical Vertebra

Vertebral element ossification between species.[6]

A comparison of vertebral element ossification between different species also in relation to Hox gene expression.[6]

  • 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[7] "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[8]

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[9]

Annulus Fibrosus

  • cells are derived from the sclerotome

Nucleus Pulposus

  • cells are derived from the notochord[9]
  • notochordal marker brachyury
  • proteoglycan rich extracellular matrix

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[8]
  • 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:[8]

  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[10]

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[11]
Chêneau Brace[12]

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. <pubmed>20544699</pubmed>
  2. <pubmed>21193993</pubmed>| PMC3055990 | {http://www.springerlink.com/content/yjn47x15520jn728/fulltext.html Childs Nerv Syst.]
  3. <pubmed>14529047</pubmed>
  4. <pubmed>1605355</pubmed>
  5. <pubmed>21822704</pubmed>
  6. 6.0 6.1 <pubmed>20956304</pubmed>| Proc Natl Acad Sci U S A.
  7. <pubmed>3688211</pubmed>
  8. 8.0 8.1 8.2 <pubmed>20214815</pubmed>| PMC2848151 | BMC Dev Biol.
  9. 9.0 9.1 <pubmed>20568241</pubmed>
  10. <pubmed>21062465</pubmed>| BMC Med Imaging.
  11. <pubmed> 23226218</pubmed>| PLoS One.
  12. <pubmed>21266084</pubmed>| PMC3037926 | Scoliosis


Reviews

<pubmed>21193993</pubmed> <pubmed>19651306</pubmed> <pubmed>19575673</pubmed> <pubmed>19247958</pubmed> <pubmed>18157900</pubmed>

Articles

<pubmed>19590010</pubmed> <pubmed>19520072</pubmed> <pubmed>19395637</pubmed>

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. (2024, March 28) Embryology Musculoskeletal System - Axial Skeleton Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Musculoskeletal_System_-_Axial_Skeleton_Development

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© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G