1Dr: Azza Zaki

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DEVELOPMENT OF THE LIMBS

Dr: Azza Zaki

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OBJECTIVES

• By the end of this lecture , the student will be able to:

Depict the origin of the limb bud. Recognize results of rotation

( innervation and dermatome )Describe the common anomalies

of limbs and digits.

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• At the end of the 4th week of development, limb buds become visible as outpocketings from the ventrolateral body wall.

• The upper limb bud appears 2 days before the lower limb bud.

Buds consist of mesenchymal core derived from the somatic layer of lateral plate mesoderm &it is covered by ectoderm cap.

Mesenchyme (mesoderm of limb bud) gives rise to bones, C.T., tendons, ligaments & blood vessels) of the limb.

5th week

Formation Of Limb Buds

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Apical Ectodermal Ridge Ectoderm at the distal

border of the limb thickens to form the apical ectodermal ridge (AER).

Apical ectodermal ridge stimulates growth & differentiation of the underlying mesoderm to form rapidly proliferated cells.

Cells farther from the influence of the AER begin to differentiate into cartilage and muscle. In this manner development of the limb proceeds proximodistally.

5th week

Ectoderm

Mesoderm

Apical ectodermal

ridge

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Lateral plate mesoderm

The mesoderm is derived from lateral plate mesoderm and some migrating myotomes.

Mesoderm

Myotomes

AER

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Formation Of Hand And Foot Plates

• In the 6th week, the terminal part of limb buds flattened to form handplates & footplates and separated from proximal segment by circular constriction.

6th week

(A)

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• Later, a second constriction divides the proximal part of the limb into 2 segments

7th week

2nd circular constriction appears to divide each limb into 3 segments.

(B)

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Formation Of Hyaline Cartilages In The Limbs

At 5th week: Mesenchymal condensation at

long axis of limbs.At 6th week: Hyaline cartilage models

(chondrification) are formed in the mesenchymal condensation.

The bones of the limbs develop in cartilage except clavicle which develops in membrane

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Ossification At 8th – 12th week,

1ry centers of ossification appear to form diaphysis (shaft) of long bones.

2ry centers of ossification for ends of long bones form epiphysis usually appear after birth.

Epiphyseal plates (hyaline cartilage) separate epiphysis from diaphysis to allow growth of bones in length.

Epiphyseal cartilage disappear after adult age.

development of the cartilaginous bones. A, At 28 days. B, At 44 days. C, At 48 days. D, At 56 days.

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cartilagecalcified cartilage

bone

epiphyseal plate

epiphyseal line

Endochondral Ossification

2o ossification

center

Fetus: 1st 2 months

AdultChildhood

Just before birth

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• In long bones an epiphyseal plate is found on each extremity.

• In smaller bones, such as the phalanges, it is found only at one extremity.

• In irregular bones, such as the vertebrae, one or more primary centers of ossification and usually several secondary centers are present.

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Development of digits (Fingers And Toes)

• Fingers and toes are formed when cell death in the AER separates this ridge into five parts.

• Continued outgrowth of the digits under the influence of the five segments of ridge ectoderm.

• Condensation of the mesenchyme to form cartilaginous digital rays, and the death of intervening tissue between the rays.

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6th week

Mesodermal condensation in the hand and foot plates results in appearance of digital rays.

H

F(B)

Digital rays divide the hand & foot plates to form fingers & toes

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7th week

A B C

The thin membranes ( webs ) in between the digital rays break down and the digits become separated by notches.

A. Digital rays

B. Webs

C. Notches

Hand or foot plate

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Illustrations of embryonic development of the limbs (32-56 days). Note that development of the upper limbs precedes that of the lower limbs.

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Rotation Of Limbs

At a later stage 7thweek, the limb buds undergo rotation.The limbs rotate in opposite directions.• The upper limb: rotates 90◦ laterally, so that the extensor muscleslie on the lateral and posterior surface and the thumbs lie laterally.• The lower limb: rotates approximately 90◦ medially, placing the extensor muscles on the anterior surface and the big toe medially.

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8th week

Limbs are extended at right angle to the trunk.2 borders: Preaxial (cephalic, big digit) Post-axial ( caudal, little digit).2 surfaces: Ventral (flexor). Dorsal (extensor(

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U.L L.L

Rotation Lateral Medial

Muscles Flexors—ant.Extensors—post.

Flexors---post.Extensors—ant.

Bones Radius---lat.Ulna---med.

Tibia---med.Fibula---lat.

Digits Thumb---lat. Big toe---med.

Rotation Of Limbs

(90) (90)

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• The muscles are derived from myotomes of somites, which migrate to limb bud carrying their nerve supply

• Around the developing bones, the mesoderm forms a muscle mass, which separates into flexor and extensor compartments.

• At end of 4th month, the muscles become strong and the baby starts to kick against the uterine wall.

• The mother starts to feel the movement of quickening.

7th week

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The upper limb bud arises opposite the lower cervical & upper thoracic segments (C5 – T1) & supplied by brachial plexus.

• The dermomyotomes (give muscles & dermis of the limbs) come from somites & migrate carrying their nerve supply from spinal cord

• The neural tube gives the motor fibers (axons of anterior horn cells)

• Neural crest cells migrate gives sensory axons, dorsal root ganglion, Schwann cells

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4th month

Finger prints develop.

3rd month

•The nails appear.

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A group of ventral rami of spinal nerves supplies the skin and muscles of each limb bud. U.L: C4-T2( brachial plexus ) L.L: L1-S4 ( lumber and sacral plexuses )

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Dermatomes of upper limb

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Dermatomes of Lower

limb

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Congenital Anomalies = Limb Defect

These anomalies are produced by drug thalidomide (for sleep = hypnotic), if used by pregnant mother during 4th & 5th weeks (most sensitive period)

1- Amelia: complete absence of the limb (melia = limb)

2- Meromelia: absence of a part of a limb3- Phocomelia (a type of meromelia): in which the

long bones are absent & a small hand or foot is attached to the trunk

4- Micromelia: all segments of the limb are very small.

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Unilateral Amelia Phacom

eliaHands & feet are attached to the trunk by irregular bones.

•Absence of one limb.

Bilateral Amelia•Complete

absence of 2 Upper limbs.

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foot is attached to the trunkBilateral phocomelia:

the hands are attached to the trunk

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• Amelia, absence of a limb. • Meromelia (Greek, meros,

part, and melos, limb), absence of part of a limb.

• A, Quadruple amelia: absence of upper and lower limbs.

• B, Meromelia of the upper limbs: the limbs are represented by rudimentary stumps.

• C, Phacomelia a form of Meromelia with the rudimentary upper limbs attached directly to the trunk.

Dr: Azza Zaki 34Congenital Talipes equinovarus of the Right foot Congenital absence of the radius

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Clubfoot or Talipes

equinovarus

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Anomalies of fingers, toes, hands or feet1. Polydactyly: extra finger or toe.2. Macrodactyly: abnormal large finger or toe.3. Ectrodactyly: absence of a digit e.g. absence of thumb.4. Syndactyly: fusion of fingers or toes.5. Cleft hand or foot: lobster-claw deformities: cleft

between 2nd & 4th metacarpal bones.6. Club foot: congenital equinovarous deformity of the foot

(the foot is inverted, adducted, & planter flexed).7. Amniotic bands may produce amputation of limb or

digit • Congenital absence of radius • Congenital dislocation of hip joint • Achondroplasia.

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Syndactyly

•Fusion of one or more digits.

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Polydactyly

In polydactyly, one or more extra digits develop. It tends to run in families. The additional digits are removed surgically.

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Bradydactyly

Shortness of the digits (fingers or toes) is the result of reduction in the length of the phalanges.

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Lobster claw

•One or more middle digit(s) is absent, the hand or foot is divided into 2 parts. In each part, the digits are fused.

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A) Polydactyly: extra digits B) Syndactyly : fused digits C) Cleft foot cleft between metatarsal bones

Polydactyly

Syndactyly

Cleft foot

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Digit amputations resulting from amniotic bands

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(incomplete fusion of fingers)

Brachydactyly due defects of phalanges

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Floating thumb due to absence of first metacarpal bone,

But the phalanges are present

Macrodactyly affecting thumb & index fingers

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Achondroplasia: common cause of dwarfism, it is autosomal dominant disease early closure of epiphyseal cartilages affect long bones short limbs. A) A child with large skull & short limbs B) & C) A girl 15 years old with dwarfism of short limb type.

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Causes of limb defects:1- Genetic: some cases results from autosomal

dominant disorders , some cases are present as component of genetic syndromes

2- Teratogenic:a) Drug & chemicals e.g. thalidomideb) Virusesc) Radiationd) Hypothermia & hyperthermia3- Mechanical:a) Amniotic bands may cause limb amputationb) Oligohydramnios may cause limb

compressionc) Uterine defect (anomalies of the uterus)

Achondroplasia : An autosomal dominant disease: (short limbs with normal trunk & head.

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Syndactyly

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Polydactyly

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Syndactyly

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Equinivarus Club

foot

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