L29 - DEVELOPMENT OF THE MUSCULOSKELETAL SYSTEM

Question 1

Define the 3 layers of mesoderm?

Answer 1

1. Paraxial mesoderm&raquo_space; somites
2. Intermediate mesoderm
3. Lateral plate mesoderm&raquo_space; embryonic connective tissue and Notochord

Question 2

Describe the differentiation of the somites on day 19?

Answer 2

Somites differentiate into:

1) Dermomyotome (dorsolateral)&raquo_space; dermatome (skin) + myotome (muscle)
2) Sclerotome

Question 3

Define the direction of migration of sclerotome and the specific differentiation in each direction?

Answer 3

1. Migrate ventrolaterally: form costal processes = precursor of ribs
2. Migrate dorsally: surround notochord to form neural arch
3. Migrate ventromedially: surround notochord:
   - Condense to form centrum of vertebral body
   - Annulus fibrosus of IVD

Question 4

Differentiation of Sclerotome cells?

Answer 4

Sclerotome cells differentiate into chondroblasts&raquo_space; form the cartilaginous precursors of:
 Bones of cranial base
 Cartilage of heart
 Axial skeleton

Question 5

Describe the formation of IVD?

Answer 5

1) Notochord in the region of vertebral bodies regresses into nucleus
pulposus

2) Sclerotome cells migrate ventromedially to form vertebral body and Annulus fibrosus

Question 6

Describe the process of forming primordial vertebral bodies?

Answer 6

Resegmentation of sclerotome:

Caudal portion of one sclerotome fuses with cranial portion of the next sclerotome (below) to form a primordium of vertebral body

each vertebra develops from 2 adjacent sclerotomes

Question 7

Describe how segmental spinal nerves can grow to innervate myotomes?

Answer 7

Resegmentation of sclerotome = splitting of sclerotomes into cranial and caudal portions = create Von Ebner’s fissures

Spinal segmental nerves grow through the fissures to reach myotomes

Question 8

Segmental spinal nerves that sprout to reach myotomes are purely motor. T or F?

Answer 8

False

Mixture of sensory and motor

Question 9

What is the final number of segmented somite myotomes?

Answer 9

42-44 pairs of somite myotomes elaborated

1 occipital and last 5-7coccygeal somites later disappear&raquo_space; final count of 35-37 pairs

 4 occipital  8 cervical  12 thoracic  5 lumbar  5 sacral

Question 10

At which week does the blood supply to limbs develop?

Answer 10

4th week

Question 11

Describe the formation of arteries that supply the upper limb.

Answer 11

C7 intersegmental artery develop into axial arteries and penetrate limb bud

Axial artery = Brachial artery + Anterior interosseous artery

New arteries = Radial and ulnar artery

Question 12

Describe the formation of arteries that supply the lower limb.

Answer 12

L5 intersegmental artery develop into axial artery to penetrate limb bud

Axial artery = Sciatic artery (obliterated during development) + popliteal artery + peroneal artery

New arteries = femoral + tibial arteries

Question 13

Describe how blood supply of limbs and venous drainage connect?

Answer 13

Axial arteries anastomose with pre-axial veins at the cranial border and Post-axial veins at the caudal border

Question 14

Describe the formation of veins for upper limbs?

Answer 14

Primordial veins = Marginal and Cardinal veins

Along cranial border: pre-axial vein develops into cephalic vein

Along caudal border: post-axial vein develops into Basilic vein

Question 15

Describe the formation of veins for lower limbs?

Answer 15

Primordial veins = Marginal and Cardinal veins

Along cranial border: pre-axial vein develops into Great saphenous vein

Along caudal border: post-axial vein develops into Small saphenous vein

Question 16

Define the somites level that develops into the limb buds?

Answer 16

 Upper limb buds – opposite the lower cervical (C5-T1) somites

 Lower limb buds – opposite the lumbosacral (L2-S3) somites

Question 17

Which germ layer are limb buds derived from?

Answer 17

 Consist of a core of mesenchyme derived from lateral plate mesoderm

 Covered by ectoderm

Question 18

Upper limb and lower limb buds develop in the same rate. T or F?

Answer 18

False

Handplate forms first at 7th week
Lower limb buds develop later at 8th week

Question 19

Define the growth modalities that determine the proximo-distal, cranial-caudal, and dorso-ventral patterning of limb development?

Answer 19

Apical ectodermal ridge (AER) determines proximo-distal patterning

Zone of polarizing activity (ZPA) determines the cranio-caudal (antero-posterior) patterning

Signals (Wnt7a, Bmpr) from dorsal and ventral ectoderms determine dorso-ventral patterning

Question 20

Describe the process of proximo-distal patterning in limb development?

Answer 20

5th week: limb tip ectoderm proliferates, thickens to form apical ectodermal ridge (AER)

AER induces adjacent mesenchymal cells to proliferate = form progress zone = causes limb to elongate, develop in proximal to distal direction

Question 21

Describe the process of cranio-caudal patterning in limb development?

Answer 21

Zone of polarizing activity (ZPA) secretes sonic hedgehog

> > higher concentration at caudal (ulnar) end develops little finger first
Selective apoptosis divides AER into 5 segments to form 5 digits

Question 22

Define the factors that determine the dorso ventral patterning of limbs?

Answer 22

dorsal and ventral ectoderms*** determine dorso-ventral patterning

 Dorsal: Wnt7a, Lmx1b
 Ventral: bone morphogenic protein (Bmpr), En1

Question 23

Describe the process of innervating developing limbs?

Answer 23

Limb buds become invaded by ventral primary rami of adjacent spinal nerves

C5-T1&raquo_space; UL
L2-S3&raquo_space; LL

 Posterior (dorsal) division = extensor muscle of limb
 Anterior (ventral) division = flexor muscle of limb

( Lateral branches = Flexor muscles of spine)

Question 24

Describe the differentiation lineages of Dermomytome?

Answer 24

1) Dermatome = dermis of skin

2) Myotome = diff. into myoblasts and then skeletal muscles
Further splits into:
a) Epimere = extensor spinal muscles: Erector spinae, Transversospinalis
b) Hypomere = Hypaxial muscles: intercostal, abdominal, strap muscles of neck, limb girdle muscles

Question 25

Compare the innervation between Epimere and Hypomere?

Answer 25

Epimere muscle derivatives and skin = Dorsal primary ramus Hypomere muscle derivatives and skin = Ventral primary ramus

Question 26

Describe the formation of Clavicle and Sternum?

Answer 26

Mesenchymal condensation for development of appendicular skeleton bones: 1) Clavicle = formed by intramembranous ossification 2) Sternum (formed by endochondral ossification): - 2 bands of lateral plate mesenchyme condense into sternal bars → fuse with each other starting cranially into a single piece of cartilage → manubrium, body, xiphoid process → vertical pairs of ossification centres appear

Question 27

When does limb rotation occur during limb development?

Answer 27

7th to 9th week

Question 28

Describe the process of limb rotation in development?

Answer 28

 Upper limb rotates laterally = elbow becomes caudal  Lower limb rotates medially = knee becomes cranial  Ventral (flexor): anterior for upper limb  Dorsal (extensor): anterior for lower limb

Question 29

When does ossification of developing limbs occur? When do secondary ossification centres appear?

Answer 29

Ossification begins in the 7th week • By 12th week, primary ossification centres present in all long bones • Most secondary ossification centres appear after birth

Question 30

Pathogenesis of sternal foramen?

Answer 30

3rd year: Ossification centre for xiphoid process appears Developmental defect: incomplete ossification centre fusion = sternal foramen

Question 31

Describe the differentiation and formation of 3 joint types?

Answer 31

Interzone mesenchyme in perichondrium differentiates into cartilage, ligaments, capsular elements of joints:  Cavitation, cavities form synovial cavity in capsule = synovial joint  Fibrocartilage = cartilaginous joint  Fibrous tissue = fibrous joint

Question 32

Define dermatome axial lines?

Answer 32

Axial lines = Where non-adjacent deratomes meet Dermatomes become non-segmental and parallel due to elongation of limb buds dragging dermatomes out

Question 33

Types of spina bifida and pathogenesis?

Answer 33

Defective fusion of 3 primary ossification centres: vertebra does not surround spinal cord, meninges Spina bifida occulta: no obvious clincial symptom Spina bifida cystica: neural tube and spine defect

Question 34

Describe the posture in Talipes equinovarus?

Answer 34

Plantarflexed, inverted foot "Club foot"

Question 35

List 4 developmental abnormalities of limbs?

Answer 35

Syndactyly and Polydactyly Spina bifida Talipes equinovarus (club foot) Developmental dysplasia of the hip (DDH) or congenital dislocation of the hip (CDH)

Question 36

Describe the abnormality in congenital dislocation of the hip?

Answer 36

Affected side is shorter in length Hip joint not aligned properly >> joint laxity means easy dislocation

Question 37

Which abnormality arises from overexpression of ZPA?

Answer 37

Polydactyly

Question 38

Which abnormality arises from poor separation of AER into 5 zones?

Answer 38

Syndactyly | Incomplete apoptosis of web between digits