Organogenesis(1). Somitogenesis
and derivatives of somites
M.A.Kai-Kai
Learning Objectives
Understand
process of somitogenesissegmental
pattern of somitomeres and somites along the neural
tube.
Review the adult derivatives of each of the three
morphological subdivisions of the
somitesdermatome, sclerotome and myotome.
 Understanding of patterns of osteogenesis from the
sclerotome.
Understanding the process of myogenesis.
Examples of congenital malformations in
development of the skeleton.
FORMATION OF THE MAMMALIAN GASTRULA - 7
Different types and locations of mesoderm are a result of different routes
of migration through and under the primitive streak
Dorsal view of embryonic disc
Rostral
EMBRYONIC
DISK
3
2a
5
1
HENSEN'S
NODE
1
Chordamesoderm
2
Paraxial mesoderm
(a) Segmented
(b) Unsegmented
3
Head mesoderm
4
Embryonic
lateral mesoderm
5
Extra-embryonic
lateral mesoderm
6
Intermediate mesoderm
4
PRIMTIVE
STREAK
6
2b
Caudal
ADULT DERIVATIVES OF THE TYPES OF MESODERM
MESODERM INTERMEDIATE
TYPE
STRUCTURE
Head
Chorda-
Notochord
MESODERM
DERIVATIVE
Head muscle, skull
cartilage
Limb muscles
Paraxial
ICM
EPIBLAST
Somites
MESODERM
Intermediate
Lateral
Axial skeleton
Trunk muscles
Dermis
Parts of kidney and
reproductive tract
Limb skeleton
Heart
Body cavity dividers
Blood cells
Amnion, Chorion
Yolk sac,
Allantois
Somitogenesis(1)
Process
of segmentationdevelopment of
axial systemvertebrae, muscles and
innervation
Somites form from paraxial mesoderm in
anterior-posterior gradient, begins at
neurulation.
Two parallel columns of mesodermal cells
form along the longitudinal axis, on each
side of the notochord and neural tube.
Transverse fissures form in the
columnsforming somitomeres in cranialcaudal direction.
First seven pairs of cranial somitomeres
form head mesenchymemigrate, form
masticatory and facial muscles.
Somite 8-46(rabbit) become segmented
into block-like somites. Number of pairs
constant for each species.
Mechanisms of compactionlaminin,
collagen and fibronectin increases cell-tocell adhesions and gap junctions.
1. Periodicitysomites
bud off in
anterior – posterior
direction(Notch and Wnt gene).
2. Fissure formationsomitomeres,
compact
3, Epithelialisationmesenchymal
cells form epithelial(Paraxis)
--synthesise extracellular matrix
--fibronectin and N-cadherin
adhesion protein rearrange outer
cells of each somite into epithelium
4.Specificationform specific
structures,according
location and expression of Hox
gene determined early in
somitogenesis.
--Ventromedialsclerotome
axial skeleton and tendons
--Dorsolateral layerdermatome, form
dermis of skin.
--Ventral layermyotome; form axial
and appendicular muscles.
Mechanism of Somitogenesis(2)
The somites are cubic blocks of
paraxial mesoderm lying on either
side of the neural tube
1&2
4&5
3
SOMITOGENESIS -3
Migration from differentiated regions of the somite give rise to dermis,
musculature and axial skeleton
SOMITE 9 OF 12 SOMITE CHICK (33 h)
Dermatome
Myotome
Sclerotome
Neural tube
Pronephric tubule
(see later)
Vertebra/axial skeleton and
tendon
Dermis
Muscles of back
Shoulder muscle
Limb muscle
Splanchnopleure
Muscles of body wall
Aorta
Somatopleure
5. Differentiationcommitted to specific cell lineage within each
region.e.g. myotomemuscles of back(close to neural tube), abaxial
muscles of body wall(farthest from neural tube).
DERIVATIVES OF SOMITES(4)
Paraxial mesoderm
Somitogenesis
Somites
Ventromedial region
Dermomyotome
Dorsolateral
region
Ventral region
Myotome
Dermatome
Myogenic cells
Dermis and supporting
tissues
Red arrows show
Regulation by
genes
Sclerotome
Chondrocytes
Skeletogenic
cells
Cartilage
Myoblasts
Axial and appendicular
Skeletal muscles
Tendon
Ossification
into bone
Osteogenesis:The development of bones(1)
Calcified organic matrix
Mesoderm
Mesenchymal cells
Osteoprogenitor cells
Osteoblasts: bone forming cells
Osteocytes: mature bone cells
Osteoclasts: a cell that breaks
down bone
Haversian Canals: surround
blood vessels & nerve cells
Skeletal System(2)
The
skeletal system consists mainly of bone and
cartilageprovides supporting framework for muscle
Bone is specialised connective composed ofcells, organic
matrix and inorganic matrix.
Bone is formed by process of oestogenesis
Cell typesosteoblasts, osteocytes and osteoclasts participate
in oestogenesis.
The organic matrix consists of type I collagen and amorphous
ground substance containing proteoglycans forms about one-third
of bone mass.
Two-thirds of bone is mineralised matrix of calcium phosphate in
form of hydroxyapatite crystals.
Bone has range of physical properties giving high degree of
flexibility, undergoes continual replacement and remodelling.
Regulation of development of the
Wnt
musculoskeletal system(3).
 Myotome induced by Wnt
genes
 Sclerotome formation is
regulated by fibroblast
growth factors(Fgf) from
myotome and sonic
hedgehog(Shh) gene
secreted by notochord and
neural tube
 Shh inhibits bone
morphogenetic
protein(BMP) gene in part
that forms tendon.
 Sox stimulates formation of
cartilage, but inhibits
scleraxis gene(sclerotome
forms tendon).
 Cartilage cells ossifies into
bone.
Somite
Shh
+
Myotome
(muscle)
(Notochord
& neural
Plate)
-
BMP
Sclerotome
Fgf
Sox
Scleraxis
Cartilage
Bone
Red arrows show
Regulation by
genes
Tendon
Osteogenesis:The development of bones(4)
Two major methods of
osteogenesis:
1.Intramembranous ossification,
no cartilagenous stage
Mesenchymal(neural crest)
condense to form
osteoblastform osteoid
matrixcacified/osteocytes(e.g
flat bones of the skull.
2. Endochondral ossification.
Mesenchymal cellscartilage
ossification into bone(e.g.long
bones).

(5)
Fig.2
Osteogenesis: Enchondral ossification(6)
Fig.3
The sclerotome cell can
become a chondrocyte
characterised by Sox9
or an osteocyte (osterix
transcription factor).
Chrondrocyte secrete
inhibitor factor that
repress the bone
pathway.
Pre-osteoblast &
Osteoblast
MYOGENESIS(1)
Myotomal
cells express transcription factor ;myogenic proteinscells
migrate to sites and induces muscle differentiation(A).
Cells proliferate and form committed progenitor myoblasts(B).
Committed myoblasts divide, induced by fibroblast growth factors.
Cell alignment under influence of cell adhesion molecules(C).
Myoblasts fuse to form myotubes (D).
And maturation of myotubes(E).
Stem muscle fibres form, begin contraction(F)
Fig.5
(Gilbert 2006)
MYOGENESIS(2)

Group into cranial-caudal axis.
 Dorsal of transverse processes of vertebraeform
epaxial muscles.
 Ventral of transverse processes form hypaxial muscles
and muscles of body wall
 Extrinsic and intrinsic muscles of limbs are derived from
myotome
 Some skeletal of limbs, cardiac and smooth muscles
derived from mesoderm
Epaxial muscles
D
V
Cervical vertebra
Transverse
process
Hypaxial muscles
Malformations(1)
Bone
Osteogenetic defectsinherited characterised by extreme fragility of bones, long
bones prone to fracture
Vertebral defects
--spinal bifida occulta/block vertebrae fusion of 2 or more
adjacent vertebrae and hemivertebrae.
--hemivertebraeonly one half develops, condition confined to thoracolumbar region
results from failure of sclerotome differentiation on one side of developing vertebral
Body
--cervical vertebraeabnormal segmentation of caudal occipital and cervical
sclerotomes result in atlantoaxial malformations
--abnormal curvature of vertebral column;
Lordosisabnormal ventral curvature
Kyphosisabnormal dorsal curvature.
--short-spined dogs results from compaction and fusion of thoracic and lumbar
vertebrae
--Stenosis of vertebral foramen constricts the spinal cord and neurological defects.
Rib defectsassociated with abnormalities of vertebral column or sternum
Sternal defects
--.incomplete fusion of paired sternal bbones during morphogenesis
--associated with ectopic heart.
Limb defects
Malformation of Limb Development(2)
Autonomy
of development produces
many abnormalities.
Limb reductionsinvolve loss of
specific parts,e.g.
1.Ameliacomplete absence of limb
2.Ectromeliapartial or complete
absence of parts, e.g.carpal ectromelia.
3.Micromelialimb reduced in size.
Limb
duplications.
1.Polydactylyextra digits
2.Whole or partial limbs
Limb and joint deformities.
1.Arthrogryposiscrooked limb,
heredity in animals.
Deficiency in gene expression
e.g.Hox and BMP.
Polydactyly
Summary
Somitogenesis
is the process of segmentation of the paraxial
mesoderm in anterior-posterior gradient, begins at neurulation.
The first seven pairs of cranial somitomeres form head
mesenchyme,migrate to specific regions and form masticatory
and facial muscles.
Somite 8-46(rabbit) become segmented into block-like somites.
Number of pairs constant for each species.
Each somite has three morphological
regions.Ventromedialsclerotome
chondrocytesform axial skeleton and syndetome from within
sclerotome form tendons. The dorsolateral layerdermatome,
form dermis of skin.Ventral layermyotome; form axial and
appendicular muscles.
The molecular mechanisms regulating osteogenesis and
myogenesis are transcription factors, growth factors,the Hox
gene, Shh,BMP, and Wnt genes.
Few examples of common congenital malformations in
development of the axial skeleton and in limb development
References
Carlson, B. M., Foundations of Embryology (6th.Edition) 1996.
McGraw-Hill inc. London. Page 393 - 424
1.
2.
Gilbert, S.F., Developmental Biology (8th. Edition) 2006. Sinauer Associates
Inc. Sunderland, Massachuetts. USA. Page 505 -527
McGeady, T.A., Quinn, P.J., Fitzpatrick, E.S., & Rayan, M.T., (2006).
Veterinary Embryology. Page 184 -203
3.
Noden, D.M., DeLaHunta, A., The Embryology of Domestic Animals.
1985, Williams & Wilkins. London. Page196 -206
4.