1 Dr: Azza Zaki

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.
Dr: Azza Zaki
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Formation Of Limb Buds
• 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.
Dr: Azza Zaki

5th week
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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.
Dr: Azza Zaki

Mesoderm

Apical ectodermal
ridge

Ectoderm

5th week
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The mesoderm is derived from lateral plate mesoderm and some migrating myotomes.

Myotomes
Mesoderm AER Lateral plate mesoderm

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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.
(A)

6th week
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• Later, a second constriction divides the proximal part of the limb into 2 segments

(B)
2nd circular constriction

7th week

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appears to divide each limb into 3 segments.

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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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Dr: Azza Zaki

Fetus: 1st 2 months

Endochondral Ossification

2o ossification center

cartilage
calcified cartilage

bone
Just before birth

epiphyseal plate
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epiphyseal line
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Childhood

Adult

• 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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Dr: Azza Zaki

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Dr: Azza Zaki

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

(B) Mesodermal condensation in the hand and foot plates results in appearance of digital rays.Zaki Dr: Azza

F

6th week
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7th week

A

B

C

Hand or foot plate

A. Digital rays

B. Webs

C. Notches

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

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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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Dr: Azza Zaki

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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 muscles lie 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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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(
Dr: Azza Zaki

8th week
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Rotation Of Limbs
U.L
Rotation Muscles Lateral (90) Flexors—ant. Extensors— post. Radius---lat. Ulna---med. Thumb---lat.

L.L
Medial (90) Flexors--post. Extensors— ant. Tibia---med. Fibula---lat. Big toe--med.
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Bones Digits

• 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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Dr: Azza Zaki

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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•The nails appear.

Finger prints develop.

3rd month
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4th month
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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 limb 3- 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 •Absence of one limb.

Bilateral Amelia •Complete absence of 2 Upper limbs.

Phacomelia
Hands & feet are attached to the trunk by irregular bones.
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Dr: Azza Zaki

Unilateral phocomelia: foot is attached to the trunk

Dr: Azza Zaki

Bilateral 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.
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Congenital Talipes equinovarus of the Right foot

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Congenital absence of the radius

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Clubfoot or Talipes equinovarus
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Anomalies of fingers, toes, hands or feet
1. 2. 3. 4. 5. Polydactyly: extra finger or toe. Macrodactyly: abnormal large finger or toe. Ectrodactyly: absence of a digit e.g. absence of thumb. Syndactyly: fusion of fingers or toes. 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 Dr: Azza Zaki 36 • Achondroplasia.

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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Polydactyly

Syndactyly

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

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Digit amputations resulting from amniotic bands
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Partial syndactly (incomplete fusion of fingers)

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Brachydactyly due defects of phalanges

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Floating thumb due to absence of first metacarpal bone, Dr: Azza Zaki But the phalanges are present

Macrodactyly
affecting thumb & index fingers 44

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

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. thalidomide b) Viruses c) Radiation d) Hypothermia & hyperthermia 3- Mechanical: a) Amniotic bands  may cause limb amputation b) Oligohydramnios  may cause limb compression c) Uterine defect (anomalies of the uterus)
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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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