Organogenesis(1). Somitogenesis Organogenesis(1). Somitogenesis and derivatives of somitesand derivatives of somites

M.A.Kai-KaiM.A.Kai-Kai

Learning Objectives Understand process of somitogenesissegmental pattern of somitomeres and somites along the neural tube. Review the adult derivatives of each of the three morphological subdivisions of the somitesdermatome, 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

HENSEN'S NODE

PRIMTIVE STREAK

EMBRYONIC DISK 1

2

3 4 5 6

Chordamesoderm

Paraxial mesoderm

Head mesoderm

Embryonic lateral mesoderm

Extra-embryonic lateral mesoderm

Intermediate mesoderm

Different types and locations of mesoderm are a result of different routes of migration through and under the primitive streak

1

2a

2b

3

4

5

6

Rostral

Caudal

Dorsal view of embryonic disc

(a) Segmented(b) Unsegmented

ADULT DERIVATIVES OF THE TYPES OF MESODERM

ICM EPIBLAST

NotochordChorda-

Head

Lateral

Paraxial SomitesAxial skeleton

Trunk muscles

Limb muscles

Intermediate

Yolk sac,Allantois

Amnion, Chorion

MESODERM

MESODERMTYPE

Dermis

Parts of kidney and reproductive tract

Head muscle, skullcartilage

MESODERMDERIVATIVE

INTERMEDIATE STRUCTURE

Heart Body cavity dividers

Limb skeleton

Blood cells

DERIVATIVES OF SOMITES(4)DERIVATIVES OF SOMITES(4)

Paraxial mesodermParaxial mesoderm SomitogenesisSomitogenesis

Ventromedial region

Sclerotome

Chondrocytes

Tendon

Dermomyotome

Myotome

Myogenic cells

Myoblasts

Axial and appendicular Skeletal muscles

Cartilage

Skeletogeniccells

Ossificationinto bone

Dermatome

Somites

Dermis and supportingtissues

Ventral regionDorsolateralregion

Red arrows showRegulation bygenes

Somitogenesis(1) Process of segmentationdevelopment of axial systemvertebrae, 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 columnsforming somitomeres in cranial-caudal direction. First seven pairs of cranial somitomeres form head mesenchymemigrate, form masticatory and facial muscles. Somite 8-46(rabbit) become segmented into block-like somites. Number of pairs constant for each species. Mechanisms of compactionlaminin, collagen and fibronectin increases cell-to-cell adhesions and gap junctions.

1. Periodicitysomites bud off in anterior – posterior direction(Notch and Wnt gene).2. Fissure formationsomitomeres, compact3, Epithelialisationmesenchymal cells form epithelial(Paraxis)--synthesise extracellular matrix--fibronectin and N-cadherinadhesion protein rearrange outercells of each somite into epithelium4.Specificationform specificstructures,accordinglocation and expression of Hoxgene determined early insomitogenesis. --Ventromedialsclerotomeaxial skeleton and tendons--Dorsolateral layerdermatome, formdermis of skin.--Ventral layermyotome; form axialand appendicular muscles.

The somites are cubic blocks of paraxial mesoderm lying on either side of the neural tube

Mechanism of Somitogenesis(2)

1&2

3

4&5

SclerotomeMyotomeDermatome

SOMITE 9 OF 12 SOMITE CHICK (33 h)

Aorta

Pronephric tubule (see later)

Splanchnopleure

Somatopleure

Neural tube

SOMITOGENESIS -3Migration from differentiated regions of the somite give rise to dermis, musculature and axial skeleton

Vertebra/axial skeleton andtendon

Muscles of back

Shoulder muscle

Limb muscle

Muscles of body wall

Dermis

5.5. DifferentiationDifferentiationcommitted to specific cell lineage within each committed to specific cell lineage within each region.e.g. myotomeregion.e.g. myotomemuscles of back(close to neural tube), abaxial muscles of back(close to neural tube), abaxial muscles of body wall(farthest from neural tube).muscles of body wall(farthest from neural tube).

(dorsolateral)

(Ventromedial)

(Ventral)

Osteogenesis:The development of bones(1)Osteogenesis:The development of bones(1)

Haversian Canals: surround Haversian Canals: surround blood vessels & nerve cellsblood vessels & nerve cells

Osteocytes: mature bone cellsOsteocytes: mature bone cells

Osteoblasts: bone forming cellsOsteoblasts: bone forming cells

Osteoclasts: a cell that breaks Osteoclasts: a cell that breaks down bonedown bone

Calcified organic matrix

Mesoderm

Mesenchymal cells

Osteoprogenitor cells

Skeletal System(2) The skeletal system consists mainly of bone and cartilageprovides supporting framework for muscle Bone is specialised connective composed ofcells, organic matrix and inorganic matrix. Bone is formed by process of oestogenesis Cell typesosteoblasts, 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 musculoskeletal system(3).

Myotome induced by Wntgenes 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.

Myotome(muscle)

Fgf Sclerotome

CartilageScleraxis

Tendon

Shh

+-BMP

SomiteWnt

Sox

Red arrows showRegulation bygenes

Bone

(Notochord& neuralPlate)

Osteogenesis:The development of bones(4)Osteogenesis:The development of bones(4) Two major methods of

osteogenesis:

1.Intramembranous ossification,

no cartilagenous stage

Mesenchymal(neural crest)

condense to form

osteoblastform osteoid

matrixcacified/osteocytes(e.g flat bones of the skull.

2. Endochondral ossification.

Mesenchymal cellscartilageossification into bone(e.g.long

bones).

Fig.2

(5)

The sclerotome cell canbecome a chondrocytecharacterised by Sox9or an osteocyte (osterix transcription factor).Chrondrocyte secreteinhibitor factor thatrepress the bone pathway.

Pre-osteoblast &Osteoblast

Fig.3

Osteogenesis: Enchondral ossification(6)

Myotomal cells express transcription factor ;myogenic proteinscells 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)

(Gilbert 2006)

MYOGENESIS(1)

Fig.5

Malformations(1)Bone Osteogenetic defectsinherited characterised by extreme fragility of bones, long bones prone to fracture Vertebral defects--spinal bifida occulta/block vertebrae fusion of 2 or moreadjacent vertebrae and hemivertebrae.--hemivertebraeonly one half develops, condition confined to thoracolumbar regionresults from failure of sclerotome differentiation on one side of developing vertebralBody--cervical vertebraeabnormal segmentation of caudal occipital and cervicalsclerotomes result in atlantoaxial malformations--abnormal curvature of vertebral column;Lordosisabnormal ventral curvatureKyphosisabnormal 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 defectsassociated 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 reductionsinvolve loss of specific parts,e.g.1. Ameliacomplete absence of limb2. Ectromeliapartial or complete absence of parts, e.g.carpal ectromelia.3.Micromelialimb reduced in size.

Limb duplications.1. Polydactylyextra digits2. Whole or partial limbs Limb and joint deformities.Arthrogryposiscrooked limb, heredity in animals. Deficiency in gene expression e.g.Hox and BMP.

Polydactyly

SummarySummarySomitogenesis 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.Ventromedialsclerotome

chondrocytesform axial skeleton and syndetome from within sclerotome form tendons. The dorsolateral layerdermatome, form dermis of skin.Ventral layermyotome; 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

ReferencesReferences1. Carlson, B. M., Foundations of Embryology (6th.Edition) 1996.McGraw-Hill inc. London. Page 393 - 424

2. Gilbert, S.F., Developmental Biology (8th. Edition) 2006. Sinauer Associates Inc. Sunderland, Massachuetts. USA. Page 505 -527

3. McGeady, T.A., Quinn, P.J., Fitzpatrick, E.S., & Rayan, M.T., (2006).Veterinary Embryology. Page 184 -203

4. Noden, D.M., DeLaHunta, A., The Embryology of Domestic Animals.1985, Williams & Wilkins. London. Page196 -206