UNSW Embryology
Musculoskeletal Development
© Dr Mark Hill (2008)
Introduction
The musculoskeletal system consists of skeletal muscle, bone, and cartilage and is mainly mesoderm in origin with some neural crest contribution.
The intraembryonic mesoderm can be broken into paraxial, intermediate and lateral mesoderm relative to its midline position. During the 3rd week the paraxial
mesoderm forms into "balls" of mesoderm paired either side of the neural groove, called somites.
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Human embryo (Stage 10), first forming somites
(white "balls" either side of neural groove) |
Human embryo (Stage 11), additional somites
(paired either side of neural tube) |
Somites appear bilaterally as pairs at the same time and form earliest at the cranial (rostral,brain) end of the neural groove and add sequentially at the caudal end.
This addition occurs so regularly that embryos are staged according to the number of somites that are present. Different regions of the somite differentiate into
dermomyotome (dermal and muscle component) and sclerotome (forms vertebral column). An example of a specialized musculoskeletal structure can be seen in the development of the limbs.
(More? limb development)
Skeletal muscle forms by fusion of mononucleated myoblasts to form mutinucleated myotubes. Bone is formed through a lengthy process involving ossification of a cartilage formed from
mesenchyme. Two main forms of ossification occur in different bones, intramembranous (eg skull) and endochondrial (eg limb long bones) ossification. Ossification continues postnatally, through puberty
until mid 20s. Early ossification occurs at the ends of long bones (More? movie mouse ossification).
Musculoskeletal and limb abnormalities are one of the largest groups of congenital abnormalities. (More? see abnormalities)
Page Links: Introduction | Some Recent Findings | Reading |
Objectives | Computer Activities | Learning activities | Podcasts |
Development Overview | Late Neural Development | Terms |
References | Glossary | Development Terms
Some Recent Findings
Mesoderm - Iimura T, Yang X, Weijer CJ, Pourquie O.
Dual mode of paraxial mesoderm formation during chick gastrulation. Proc Natl Acad Sci U S A. 2007 Feb 13; (More? Week 3 - Gastrulation | Chicken Development)
"The skeletal muscles and axial skeleton of vertebrates derive from the embryonic paraxial mesoderm.
...fate mapping further shows that the paraxial mesoderm territory in the epiblast is regionalized along the anteroposterior axis as in lower vertebrates.
These observations suggest that the mechanisms responsible for paraxial mesoderm formation are largely conserved across vertebrates."
Pattern of Pax7 expression during myogenesis in the posthatch chicken establishes a model for satellite cell differentiation and renewal
Orna Halevy etal., Developmental Dynamics (2004) 231:489 - 502
Reading
- 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
Objectives
- Name 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 (consult Histology
Manual).
- Enumerate 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. (Refer to Introductory
Anatomy notes).
- Briefly summarise the development of the limbs.
- Describe the developmental aberrations responsible for the following malformations:
selected growth plate disorders; congenital dislocation of the hip; scoliosis;
arthrogryposis; and limb reduction deformities.
Computer Activities
UNSW Embryology:
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.
Video
Development Overview
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.
Mesoderm Development
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.
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.
Note intraembryonic
coelomic cavity communicates with
extraembryonic coelom through portals
(holes) initially on lateral margin of
embryonic disc.
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
Somite Development
Mesoderm beside the notochord (axial mesoderm) thickens, forming the
paraxial mesoderm as a pair of strips along the rostro-caudal axis.
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.
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.
Next section Limb Development
Limb Development
Also notes page on limb development
Carnegie stage 13/14 Embryo Serial Sections (Pig)
Serial section D3 (rotated 90 degrees) Mouseover to identify structures
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.
References
Note - See also other specific musculoskeletal notes pages: References | Abnormalities | Somite |
Limb | Axial Skeleton | Skull |
Bone | Human Bone | Skeletal Muscle |
Molecular
Reviews
Baron R, Rawadi G, Roman-Roman S.
Wnt signaling: a key regulator of bone mass. Curr Top Dev Biol. 2006;76:103-27.
Pogue R, Lyons K.
BMP signaling in the cartilage growth plate. Curr Top Dev Biol. 2006;76:1-48.
Articles
Wasteson P, Johansson BR, Jukkola T, Breuer S, Akyürek LM, Partanen J, Lindahl P.
Developmental origin of smooth muscle cells in the descending aorta in mice. Development. 2008 May;135(10):1823-32.
Nissim S, Allard P, Bandyopadhyay A, Harfe BD, Tabin CJ.
Characterization of a novel ectodermal signaling center regulating Tbx2 and Shh in the vertebrate limb. Dev Biol. 2006 Dec 9;
Search PubMed: Feb 2007 "musculoskeletal development" 35,405 reference articles of which 3,514 were reviews.
Search PubMed Now: musculoskeletal development |
mesoderm development
(More? PubMed- Medline)
Selected Lists of References from PubMed March 1999 search results are available for Department of Anatomy computers without internet
access: Somite Reviews | Somitogenesis Abstracts | Mesoderm Review List
Computers with internet access can search from either Below or directly from PubMed Internet Access
Glossary of Terms
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Development Terms
- acetabulum-
- amnion-
- anlage- (Ger. )
primordium, structure or cells which will form a
future structure.
- annulus
fibrosus- the circularly arranged fibers
(derived from sclerotome)that together with the
nucleus pulposus (derived from notochord) form
the intervertebral
disc (IVD) of the vertebral column.
- apical ectodermal ridge-
(=AER) specialized region of ectoderm at the
tip of the growing limbbuds that specifies
proximo/distal axss of limb development
- aponeurosis-
- apoptosis- the process of programmed cell death. In development of the limbs occurs in the "paddle" if both the hand and foot, generating the separated digits.
Occurs in many tissues of the embryo and adult.
- axial mesoderm (=notochord)
- axillary fossa the future "armpit" region
- brachial
plexus- mixed spinal nerves innervating the
upper limb form a complex meshwork
(crossing).
- cartilage-
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
sclerotome.
- clavicle- (L.
little key) bone which locks sholder to
body.
- cloacal
membrane- at caudal (anal) end of
gastrointestinal tract (GIT) where surface
ectoderm and GIT endoderm meet forms the
openings for GIT, urinary, reproductive tracts.
(see also buccopharyngeal
membrane)
- connective tissue-
- costotransverse-
- costovertebral-
- dermatome-
- dermomyotome- dorsolateral half of each
somite that forms the dermis and muscle.
- dystrophy-
- 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
the embryo.
- ectodermal
ring- the thickened ring of ectoderm seen
dorsally in the early (stage13/14) embryo
adjacent to the dermatome. Ectoderm ventrally is
relatively thin, gaining its dermatome component
at a later stage.
- endochondrial
ossification- the process of replacement of
the cartilagenous framework by osteoblasts with
bone.
- epaxial myotome-
the dorsal portion of the myotome that generates
dorsal skeletal muscles (epaxial muscles).
- epimysium-
- erector
spinae-
- external
oblique m.-
- extracellular matrix-
material secreted by and surrounding cells.
Consists if fibers and ground substance.
- ependyma-
- epiblast- the
layer (of the bilaminar embryo) that generates
endoderm and mesoderm by migration of cells
through the primitive streak. The remaing cells
form ectoderm.
- extensor-
- fascia-
- fascicle-
(=bundle)
- femur-
- 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.
- flexor-
- fossa-
- gracilis
m.-
- growth
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)
- hox-
(=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.
- humerus-
- hypaxial
myotome- the ventral portion of the myotome
that generates ventral skeletal muscles
(hypaxial muscles).
- inguinal
fossa- the region of the lower limb ajacent
to flexor surface (exuivilant to the axillary
fossa of the upper limb).
- intercostal-
the region between adjacent ribs, usually
comprising intercostal muscles and connective
tissue.
- 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-
- ischium-
- lumbar
plexus- mixed spinal nerves innervating the
lower limb form a complex meshwork
(crossing).
- mesenchyme-
- 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
extraembryonic mesoderm.
- metacarpal
cartilage-
- muscle- 3 main
types of muscle (smooth, cardiac and skeletal)
all derived from mesoderm but different
regions.
- myotome-
- 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
muscles).
- neural
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
the somites.
- neural
tube- neural plate region of ectoderm
pinched off to form hollow ectodermal tube above
notochord in mesoderm.
- neuropore-
opening at either end of neural tube:
cranial=rostral=anterior, caudal=posterior. The
cranial neuropore closes (day 25) approx. 2 days
(human) before caudal.
- nucleus
pulposus- central region of intervertebral
discs of the spinal cord derived from the
notochord.
- 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.
- otocyst- (=otic
vesicle) sensory placode
which sinks into mesoderm to form spherical
vesicle (stage 13/14 embryo) that will form
components of the inner ear.
- patella-
- 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
domain.
- pedicle-
- perichondrium-
- perimysium-
- phalangeal
cartilage-
- pharyngeal arches- (=branchial
arches, Gk. gill) form structures of the head.
Six arches form but only 4 form any structures.
Each arch has a pouch, membrane and cleft.
- pharynx-
uppermost end of GIT, beginning at the
buccopharyngeal membrane and at the level of the
pharyngeal arches.
- phocomelia-
- quadratus
lumborum m.-
- quadriceps
m.-
- rectus
abdominal m.-
- sacrum-
- scapula-
- sclerotome-
ventromedial half of each somite that forms the
vertebral body and intervertebral disc.
- segmentation-
to break a solid structure into a number of
usually equal size pieces.
- serosa-
- spinal
canal- the mature space in the core of the
spinal cord (filled with CSF) formed from the
original lumen of the neural tube.
- spinal
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.
- spinal
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.
- spinal
nerve- mixed nerve (motor and sensory)
arising as lateral pairs at each vertebral
segmental level.
- somatic
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).
- somitic
mesoderm-
- somitocoel- a
transient cavity that appears within each of the
the early forming somites then is lost.
- somitogenesis-
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
formation.
- sternum-
- syndactyly-
fusion of digits.
- tarsal-
- Tbx- T-box genes
(transcription factor) involved in mouse
forelimb (Tbx4) and hindlimb (Tbx5)
specification.
- tibia-
- transcription
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).
- transverse
abdominal m.-
- trochanter-
- vertebral
body- formed by centrum, vertebral arch,
facets for ribs. It is the mature vertebral
structure formed by the 5 secondary ossification
centers after puberty.
- vertebral
column- name given to the complete structure
formed from the alternating segments of vertebra
and intervertebral discs which support the
spinal cord.
- vertebral
foramen- the dorsal cavity within each
vertebra, generated by the vertebral arch that
surrounds the spinal cord.
- vertebral
canal-
- 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.
- zone of polarizing
activity- (zpa) dorsal region with forming
limbbud mesenchyme that secretes shh and
regulates limb axis formation.
Glossary of Terms
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UNSW Embryology ISBN: 978 0 7334 2609 4
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Comments
The mesoderm forms nearly all the connective tissues of the musculoskeletal system. Each tissue (cartilage, bone, and muscle)
goes through many different mechanisms of differentiation.
These note therefore have many different pages covering each of tissue, as
well as information about limb development. Use the left hand menu to go to a specific topic of interest.
Please email Dr Mark Hill if you wish to make a comment about this current project.
