Musculoskeletal Development - Axial Skeleton
© Dr Mark Hill (2011)
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.
Cross-section of developing vertebra (longitudinal of axial skeleton).
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, these vertebral elements are made up of rostro-caudally: 7 cervical, 12 thoracic, 5 lumbar, 1 sacrum, coccyx.
Skeletal ossification continues postnatally, through puberty until mid 20s.
Abnormalities of vertebral column development can lead to defects including scoliosis (More? Scoliosis).
There are also additional notes covering molecular regulation of vertebral column development (More? Molecular - Vertebral Column).
Introduction | Some Recent Findings | Development Overview | Somites and Sclerotome |
References | WWW Links | Glossary
Some Recent Findings
Pickett EA, Olsen GS, Tallquist MD. Disruption of PDGFRalpha-initiated PI3K activation and migration of somite derivatives leads to spina bifida. Development. 2008 Feb;135(3):589-98.
"Genetic disruption of platelet-derived growth factor receptor (PDGFR) alpha results in spina bifida, but the underlying mechanism has not been identified. ...results indicate that PDGFRalpha downstream effectors, especially PI3K, are essential for cell migration of a somite-derived dorsal mesenchyme and disruption of receptor signaling in these cells leads to spina bifida."
Somites and Sclerotome
Early stage 10 human embryo showing first forming somites laterally and neural groove in the midline.
Later stage 11 human embryo showing additional somites
Somites appear bilaterally as pairs at the same time and
form earliest at the cranial end (rostral, brain) of the neural groove
and add sequentially at the caudal end.
Carnegie stage 13/14 Embryo Serial Section showing spinal cord (top), with sclerotome forming vertebral body (pale region below spinal cord).
Cross-section of developing vertebra (longitudinal of axial skeleton).
Centre of the image shows initial vertebra "bony collar" (in red) forming, either side of which
is the original cartilage (blue) "template", outside of that again are the 2 intervertebral discs (not shown).
Human Embryology (3rd ed.) Larson Ch11 p311-339
The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud Ch15,16: p405-423, 426-430
Before We Are Born (5th ed.) Moore and Persaud Ch16,17: p379-397, 399-405
Essentials of Human Embryology Larson Ch11 p207-228
Human Embryology, Fitzgerald and Fitzgerald
Human Embryology and Developmental Biology, (3rd ed.) Carlson Ch9,10: p173-193, 209-222
These Lecture links are to current and historic courses and may also link directly to PDF version of Lecture slides
(educational use only).
ANAT2300 (2004) Lecture 6 Mesoderm
ANAM1006 (2003) Musculoskel Development Lab
ANAT2300 (2004) Lecture 7 Bone (view)
ANAT2300 (2004) Lecture 7 Bone (print)
Human Embryology Movies:
Fate of the Somite (315Kb)
Embryo Images Unit:
Body Cavities, Musculoskeletal &Limb Development
Embryo Images Online External links below require Internet connection.
Developmental Biology (6th ed.) Gilbert:
NCBI Bookshelf external links below require Internet connection.
Below is a very brief overview using simple figures of 3 aspects of
early musculoskeletal development covering : Mesoderm then Somite
and Limb development
More detailed overviews are shown on other notes pages (Mesoderm and Somite,
Vertebral Column, Limb) in combination with serial sections and Carnegie images.
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
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.
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.
coelomic cavity communicates with
extraembryonic coelom through portals
(holes) initially on lateral margin of
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.
Next Somite Development
Mesoderm beside the notochord (axial mesoderm) thickens, forming the
paraxial mesoderm as a pair of strips along the rostro-caudal axis.
towards the rostral end, begins to segment forming the first
are then sequentially added caudally. The somitocoel
is a cavity forming in early somites, which is lost as the somite matures.
Cells in the somite differentiate medially to form the sclerotome (forms
vertebral column) and laterally to form the dermomyotome.
The dermomyotome then forms the dermotome (forms dermis) and myotome (forms muscle).
Neural crest cells migrate beside and through somite.
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.
Reviews | Articles | Search NCBI Bookshelf | Search PubMed
Kaplan KM, Spivak JM, Bendo JA.
Embryology of the spine and associated congenital abnormalities.
Spine J. 2005 Sep-Oct;5(5):564-76.
Sclerotome development and morphogenesis: when experimental embryology meets genetics.
Int J Dev Biol. 2005;49(2-3):301-8.
Christ B, Huang R, Wilting J.
The development of the avian vertebral column. Anat Embryol (Berl). 2000 Sep;202(3):179-94.
Erwin WM, Inman RD.
Notochord cells regulate intervertebral disc chondrocyte proteoglycan production and cell proliferation.
Spine. 2006 May 1;31(10):1094-9.
Bird NC, Mabee PM.
Developmental morphology of the axial skeleton of the zebrafish, Danio rerio (Ostariophysi: Cyprinidae).
Dev Dyn. 2003 Nov;228(3):337-57.
Search NCBI Bookshelf:
Bookshelf - vertebra development
Molecular Cell Biology - Effect of loss-of-function mutations in Hox-4 paralogs on development of cervical vertebrae in mice
Search PubMed: Search May 2006 "vertebra development" 4,001 reference articles of which 386 were reviews.
Search term = vertebra development
Glossary of Terms
A | B | C | D | E |
F | G | H | I | J |
K | L | M | N | O |
P | Q | R | S | T |
U | V | W | X | Y | Z | Numbers | Old Glossary
fibrosus the circularly arranged fibers
(derived from sclerotome)that together with the
nucleus pulposus (derived from notochord) form
disc (IVD) of the vertebral column.
- axial mesoderm (=notochord)
connective tissue from mesoderm in the embryo
forms initial skeleton replaced by bone. In
adult, found on surface of bone joints.
- centrum the
primordium of the vertebral
body formed initially by the
- clavicle (L. little key) bone which locks shoulder to
- connective tissue-
- dermomyotome- dorsolateral half of each
somite that forms the dermis and muscle.
- ectoderm the
layer (of the 3 germ cell layers) which form the
nervous system from the neural tube and neural
crest and also generates the epithelia covering
ossification the process of replacement of
the cartilagenous framework by osteoblasts with
- epaxial myotome
the dorsal portion of the myotome that generates
dorsal skeletal muscles (epaxial muscles).
- extracellular matrix
material secreted by and surrounding cells.
Consists if fibers and ground substance.
- fibroblast growth
factors (FGF) a family of at least 10
secreted proteins that bind membrane tyrosine
kinase receptors. A patterning switch with many
different roles in different tissues. (FGF8 =
androgen-induced growth factor (AIGF)
- fibroblast growth factor
receptor- receptors comprise a family of at
least 4 related but individually distinct
tyrosine kinase receptors (FGFR1- 4). They have
a similar protein structure, with 3
immunoglobulin-like domains in the extracellular
region, a single membrane spanning segment, and
a cytoplasmic tyrosine kinase domain.
factor usually a protein or peptide that
will bind a cell membrane receptor and then
activates an intracellular signaling pathway.
The function of the pathway will be to alter the
cell directly or indirectly by changing gene
expression. (eg shh)
(=homeobox) family of
transcription factors that bind DNA and activate
gene expression. Expression of different Hox
genes along neural tube defines rostral-caudal
axis and segmental levels.
myotome the ventral portion of the myotome
that generates ventral skeletal muscles
the region between adjacent ribs, usually
comprising intercostal muscles and connective
- intervertebral disc
(IVD) the annulus fibrosus+nucleus pulposus
together form the intervertebral disc (IVD) of
the vertebral column. This is the flexible
region between each bony vertebra that allows
the column to be bent.
- intervertebral foramina-
plexus mixed spinal nerves innervating the
lower limb form a complex meshwork
- mesoderm the
middle layer of the 3 germ cell layers of the
embryo. Mesoderm outside the embryo and covering
the amnion, yolk and chorion sacs is
- myoblast the
undifferentiated mononucleated muscle cells that
will fuse together to form a multinucleated
myotube, then mature into a muscle fibre.
- MyoD transcription
factor involved in the determination of muscle
cells in the somite. A basic helix-loop-helix
factor which binds DNA.
- myotome the
portion of the dermamyotome that generates
skeletal muscle. Has 2 components epaxial
(dorsal muscles ) hypaxial (ventral
crest cell region at edge of neural plate,
then atop the neural folds, that remains outside
and initially dorsal to the neural tube when it
forms. These paired dorsal lateral streaks of
cells migrate throughout the embryo and can
differentiate into many different cell
types(=pluripotential). Those that remain on the
dorsal neural tube form the sensory spinal
ganglia (DRG). Neural crest cells migrate into
tube neural plate region of ectoderm
pinched off to form hollow ectodermal tube above
notochord in mesoderm.
opening at either end of neural tube:
cranial=rostral=anterior, caudal=posterior. The
cranial neuropore closes (day 25) approx. 2 days
(human) before caudal.
pulposus central region of intervertebral
discs of the spinal cord derived from the
- notochord rod
of cells lying in mesoderm layer ventral to the
neural tube, induces neural tube and secretes
sonic hedgehog which "ventralizes" the neural
tube and may influence somite development.
- Pax name derived
from Drosophila gene 'paired' (prd) the 'paired
box' is a amino end 124 amino-acid conserved
domain (signature aa 35-51:
P-C-x(11)-C-V-S). Transcription factor of
the helix-turn-helix structural family, DNA
binding, and activating gene expression. In
human, nine member proteins from Pax-1 to Pax-9.
Regulate differentiation of many different
tissues. Some members of the family (PAX3, PAX4,
PAX6, PAX7) also contain a functional homeobox
ventromedial half of each somite that forms the
vertebral body and intervertebral disc.
to break a solid structure into a number of
usually equal size pieces.
cord caudal end of neural tube that does
not contribute to brain. Note: the process of
secondary neuralation contributes the caudal end
of the spinal cord.
ganglia (=dorsal root ganglia, drg) sensory
ganglia derived from the neural crest lying
laterally paired and dorsally to the spinal cord
(in the embryo found ventral to the spinal
cord). Connects centrally with the dorsal horn
of the spinal cord.
nerve mixed nerve (motor and sensory)
arising as lateral pairs at each vertebral
mesoderm derived from lateral mesoderm
closest to the ectoderm and separated from other
component of lateral mesoderm (splanchnic, near
endoderm) by the intraembryonic coelom.
- somite segmental
block (ball) of mesoderm formed from paraxial
mesoderm adjacent to notochord (axial mesoderm).
Differentiates to form initially sclerotome and
dermamyotome (then dermotome and myotome).
- somitocoel a
transient cavity that appears within each of the
the early forming somites then is lost.
the process of segmentation of the paraxial
mesoderm to form "mesoderm balls" beginning
cranially (humans day20) and extending caudally
at 1 somite/90 minutes until approx. 44 pairs
have been formed.
- sonic hedgehog
(=shh) secreted growth factor that binds patched
(ptc) receptor on cell membrane. SHH function is
different for different tissues in the embryo.
In the nervous system, it is secreted by the
notochord, ventralizes the neural tube, inducing
the floor plate and motor neurons. In the Limb
it is secreted by the zone of polarizing
activity (ZPA) organizing limb axis
- Tbx T-box genes
(transcription factor) involved in mouse
forelimb (Tbx4) and hindlimb (Tbx5)
factor a factor (protein or protein with
steroid) that binds to DNA to alter gene
expression, usually to activate. (eg steroid
hormone+receptor, Retinoic acid+Receptor, Hox,
Pax, Lim, Nkx-2.2).
body formed by centrum, vertebral arch,
facets for ribs. It is the mature vertebral
structure formed by the 5 secondary ossification
centers after puberty.
column name given to the complete structure
formed from the alternating segments of vertebra
and intervertebral discs which support the
foramen the dorsal cavity within each
vertebra, generated by the vertebral arch that
surrounds the spinal cord.
- Wnt7a The
designation 'Wnt' was derived from 'wingless'
and 'int'. The Wnt gene was first defined as a
protooncogene, int1. Humans have at least 4 Wnt
genes: Wnt7a gene is at 3p25 encoding a 349aa
secreted glycoprotein. A patterning switch with
different roles in different tissues. The
mechanism of Wnt distribution (free diffusion,
restricted diffusion and active transport) and
all its possible cell receptors are still being
determined. At least one WNT receptor is
Frizzled (FZD). The Frizzled gene family encodes
a seven-transmembrane receptor.
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