1. Organogenesis(1). Somitogenesis and derivatives of somites
M.A.Kai-Kai

2. 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.

3. 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 3 1
Chordamesoderm
DISK 2a 2
Paraxial mesoderm 5 1
(a) Segmented
(b) Unsegmented
HENSEN'S 3
Head mesoderm
NODE 4
Embryonic 4
lateral mesoderm
PRIMTIVE
STREAK 5
Extra-embryonic
lateral mesoderm 6 6
Intermediate mesoderm 2b
Caudal

4. ADULT DERIVATIVES OF THE TYPES OF MESODERM
INTERMEDIATE
STRUCTURE
MESODERM
DERIVATIVE
Head
Head muscle, skull
cartilage
Chorda-
Notochord
Limb muscles
Axial skeleton
Paraxial
Somites
Trunk muscles
ICM
EPIBLAST
MESODERM
Dermis
Intermediate
Parts of kidney and
reproductive tract
Limb skeleton
Lateral
Heart
Body cavity dividers
Blood cells
Amnion, Chorion
Yolk sac,
Allantois

5. 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 cranial-caudal 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-to-cell adhesions and gap junctions.

6. Mechanism of Somitogenesis(2)
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.
The somites are cubic blocks of paraxial mesoderm lying on either side of the neural tube
1&2
4&5 3

7. SOMITOGENESIS -3
Migration from differentiated regions of the somite give rise to dermis, musculature and axial skeleton
Vertebra/axial skeleton and
tendon
SOMITE 9 OF 12 SOMITE CHICK (33 h)
Dermatome
Dermis
Neural tube
Muscles of back
Shoulder muscle
Limb muscle
Muscles of body wall
Myotome
Sclerotome
Pronephric tubule
(see later)
Splanchnopleure
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).

8. DERIVATIVES OF SOMITES(4)
Paraxial mesoderm Somitogenesis
Somites
Ventromedial region
Dermomyotome
Sclerotome
Ventral region
Dorsolateral
region
Myotome
Chondrocytes
Dermatome
Skeletogenic
cells
Myogenic cells
Cartilage
Dermis and supporting
tissues
Myoblasts
Tendon
Red arrows show
Regulation by
genes
Ossification
into bone
Axial and appendicular
Skeletal muscles

9. Osteogenesis:The development of bones(1)
Calcified organic matrix
Mesoderm
Mesenchymal cells
Osteoprogenitor cells
Osteoblasts: bone forming cells
Osteocytes: mature bone cells
Haversian Canals: surround blood vessels & nerve cells
Osteoclasts: a cell that breaks down bone

10. 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.

11. Regulation of development of the musculoskeletal system(3).
Somite
Regulation of development of the musculoskeletal system(3).
Wnt
Shh +
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.
(Notochord
& neural
Plate) -
BMP
Myotome
(muscle)
Sclerotome
Fgf
Sox
Scleraxis
Cartilage
Bone
Red arrows show
Regulation by
genes
Tendon

12. 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).

13. (5)
Fig.2

14. 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

15. 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)

16. 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
Cervical vertebra D
Transverse
process V
Hypaxial muscles

17. 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

18. Malformation of Limb Development(2)
Autonomy of development produces many abnormalities.
Limb reductionsinvolve loss of specific parts,e.g.
Ameliacomplete absence of limb
Ectromeliapartial or complete absence of parts, e.g.carpal ectromelia.
3.Micromelialimb reduced in size.
Limb duplications.
Polydactylyextra digits
Whole or partial limbs
Limb and joint deformities.
Arthrogryposiscrooked limb, heredity in animals.
Deficiency in gene expression e.g.Hox and BMP.
Polydactyly

20. 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

21. References
Carlson, B. M., Foundations of Embryology (6th.Edition) 1996.
McGraw-Hill inc. London. Page
Gilbert, S.F., Developmental Biology (8th. Edition) Sinauer Associates Inc. Sunderland, Massachuetts. USA. Page
McGeady, T.A., Quinn, P.J., Fitzpatrick, E.S., & Rayan, M.T., (2006).
Veterinary Embryology. Page
Noden, D.M., DeLaHunta, A., The Embryology of Domestic Animals.
1985, Williams & Wilkins. London. Page