Lecture 1: Embryology Limbs

Question 1

Between which weeks in embryonic development does limb development occur?

Answer 1

Weeks 4-8

Question 2

When do limb buds first appear?

Answer 2

End of week 4

Question 3

Where do limb buds first appear?

Answer 3

As outpouchings from the ventrolateral body wall

Question 4

Do the upper limbs develop a few days ahead or behind the lower limbs?

Answer 4

Ahead

As with most embryological development, cranial development is faster than caudal development

Question 5

What are the 3 layers in the trilaminar embryonic disc?

Answer 5

Ectoderm
Mesoderm
Endoderm

Question 6

What 3 parts is the mesoderm divided into to?

Answer 6

Paraxial mesoderm (closest to notochord)
Intermediate mesoderm
Lateral plate mesoderm

Question 7

Which 2 germ layers contribute to limb development?

Answer 7

Ectoderm and mesoderm

Question 8

What do the limb buds initially consist of?

Answer 8

A core of tissue derived from lateral plate mesoderm

Surrounded by ectoderm which forms the overlying skin - the epidermis

Question 9

What does the lateral plate mesoderm core of the limb buds differentiate into and what does this go on to form?

Answer 9

Differentiates into mesenchyme

This mesenchyme will form the bones and connective tissue of the limbs

Question 10

From what part of the mesoderm is the skeletal muscle of the limbs derived from?

Answer 10

Paraxial mesoderm

Question 11

What does the paraxial mesoderm divide into either side of the neural tube?

Answer 11

Somites

Question 12

The somites divide into 2 parts, what is the ventral part called and what does this go on to form?

Answer 12

Ventral part of the somites forms the sclerotome which forms the vertebral column

Question 13

The somites divide into 2 parts what is the dorsolateral part called and what does this go on to form?

Answer 13

Dorsolateral part forms the dermomyotome
The dermamyotome divides into the dermatome and the myotome
The dermatome gives rise to the dermis of the skin and the myotome gives rise to the skeletal muscles

Question 14

The myotome derived from the somites differentiates to form 2 components, what are they called?

Answer 14

1) Dorsal epimere

2) Ventral hypomere

Question 15

What does the dorsal epimere from the myotome form and what is it innervated by?

Answer 15

Forms the back muscles which are innervated by the dorsal rami of the spinal nerves

Question 16

What does the ventral hypomere of the myotome form and what is it innervated by?

Answer 16

Forms the muscles of the thoracic and abdominal walls and the muscles of the limbs which are innervated by the ventral rami of the spinal nerves

Question 17

The muscles of the limbs are formed from what part of the myotome?

Answer 17

Ventral hypomere

Question 18

At how many weeks has the myotome differentiated into the 2 components the epimere and hypomere?

Answer 18

5 weeks

Question 19

The skeletal muscle of the upper limb is derived from the hypomere from which vertebral level?

Answer 19

C5-C8

Question 20

The skeletal muscle of the lower limb is derived from the hypomere from which vertebral level?

Answer 20

L3-L5

Question 21

As the hypomeres migrate to the limb they divide into what 2 parts?

Answer 21

Anterior condensation

Posterior condensation

Question 22

At how many weeks has the hypomere migrated to the limbs and divided into an anterior and posterior condensation?

Answer 22

7 weeks

Question 23

What do the anterior and posterior condensations of the hypomere form in the upper limb?

Answer 23

Posterior - Extensors and supinators of the upper limbs

Anterior - Flexors and pronators of the upper limb

Question 24

What do the anterior and posterior condensations of the hypomere form in the lower limb?

Answer 24

Posterior - Extensors and abductors of lower limb

Anterior - Flexors and adductors of lower limb

Question 25

The upper limb is innervated by what plexus?

Answer 25

Brachial plexus

Question 26

The brachial plexus receives nerves from which vertebral level?

Answer 26

C5-T1

Question 27

The lower limb is innervated by which plexus?

Answer 27

Lumbosacral plexus

Question 28

The lumbosacral plexus receives nerves from which vertebral level?

Answer 28

L4-S3

Question 29

Why do anterior and posterior compartments of the limbs have different nerve supplies?

Answer 29

As the ventral rami of the spinal nerves migrate into the limb bud with the developing musculature, they split into anterior and posterior branches Thus an anterior branch supplying the muscles of the anterior compartment And a posterior branch supplying the muscles of the posterior compartment

Question 30

Between which weeks does limb rotation occur?

Answer 30

Between 6th and 8th weeks

Question 31

Which way do the upper limbs rotate? Where do the flexors ultimately lie?

Answer 31

90 degrees laterally | Flexors lie anteriorly

Question 32

Which way do the lower limbs rotate? Where do the flexors ultimately lie?

Answer 32

90 degrees medially | Flexors lie posteriorly

Question 33

What causes the sensory dermatomes to spiral around the limbs?

Answer 33

Limb rotation between weeks 6 and 8

Question 34

Which 3 axis does limb development occur along?

Answer 34

1) Proximodistal - outwards from the body 2) Craniocaudal - ie the thumb is most cranial and the little finger most caudal 3) Dorsoventral - the palm of the hand and the sole of the foot are ventral and the knuckle side of the hand/foot are dorsal

Question 35

What is the name of the growth factor secreted by the lateral plate mesoderm forming the mesenchymal core, and what does this cause the development of?

Answer 35

Secretes fibroblastic growth factor 10 (Fgf 10) This induces the thickening of the overlying ectoderm over the tip of the limb bud to form the apical ectodermal ridge - AER

Question 36

What is secreted by the apical ectodermal ridge and what does this cause?

Answer 36

Fibroblastic growth factors 4 and 8, (Fgf 4 and 8) This causes rapid proliferation of mesenchymal cells underlying the AER - the progress zone The progress zone maintains proximodistal outgrowth of the limb

Question 37

What 3 growth factors are involved in controlling the proximodistal outgrowth of the developing limb and wat are they secreted by?

Answer 37

Fibroblastic growth factor 10 - mesenchyme (lateral plate mesoderm) Fibroblastic growth factors 4 and 8 - Apical ectodermal ridge

Question 38

Which experiment proves the role played by the AER in controlling the proximodistal growth of the developing limb?

Answer 38

In a chick If the AER is removed from the developing limb then this hastens the proximodistal growth of the developing limb and it will not develop further

Question 39

Which experiment proves the role of Fgf 4,8 and 10 in limb development?

Answer 39

If beads soaked in Fgf are implanted in a developing embryo close to the normal sights of limb development this results in supernumerary limbs

Question 40

How is dorsoventral patterning controlled in limb development?

Answer 40

The dorsal ectoderm expresses Wnt 7 which induces the development of nails and knuckles The ventral mesoderm expresses Engrailed 1 which inhibits Wnt 7 and encourages the development of palms and soles

Question 41

Which 2 proteins are involved in the control of dorsoventral patterning in the developing limb?

Answer 41

Wnt 7 | Engrailed 1

Question 42

Which experiment proves the role of Wnt 7 in dorsoventral patterning in the developing limb?

Answer 42

Wnt7 knockout mice form foot pads on the dorsal aswell as the ventral wall

Question 43

What is the name of the region involved in controlling the craniocaudal limb development and where is it located?

Answer 43

Called the zone of polarising activity (ZPA) | Small region of mesenchyme located in the caudal region of the limb bud

Question 44

Which protein is expressed by the ZPA that controls craniocaudal limb development?

Answer 44

Sonic Hedgehog (Shh)

Question 45

How does the ZPA and Shh control craniocaudal limb development?

Answer 45

Shh is expressed by the ZPA Shh diffuses in the cranial direction as it does so the concentration decreases High concentrations of Shh induces formation of caudal structure eg. little finger and 4th digit/little toes Low concentrations induce the formation of cranial structures eg thumbs/toes

Question 46

Which experiment proves the role of the ZPA and Shh in craniocaudal limb development?

Answer 46

Transplantation of the ZPA induces mirror image polydactyl | ie. put an extra ZPA in the cranial region you get little fingers both cranially and caudally

Question 47

In which week do the terminal regions of the limb buds flatten to form hand and foot plates?

Answer 47

Week 6

Question 48

From the flattened hand and foot plates how are the fingers formed?

Answer 48

Formed by apoptosis This apoptosis splits the AER into 5 parts which continue to grow and form fingers Apoptosis continues in the intervening tissues between digits

Question 49

What is amelia and how does it occur?

Answer 49

Complete absence of one or more limbs | early loss of Fgf signalling

Question 50

What is meromelia and how does it occur?

Answer 50

Partial absence of a limb | later or partial loss of Fgf signalling

Question 51

What is phocomelia and how does it occur?

Answer 51

Digits develop prematurely Proximal elements of the limbs are absent aka. flipper limb Can be due to genetic factors or teratogens eg. Thalidomide which inhibits Fgf 10 and Fgf 8 expression

Question 52

Thalidomide inhibits the expression of which growth factors?

Answer 52

Fgf 10 and Fgf 8

Question 53

Why is phocomelia due to thalidomide still seen in Brasil?

Answer 53

Thalidomide is used to treat leprosy and HIV and there is often a lack of education for mothers regarding the danger to babies

Question 54

What is syndactyly and what is it caused by?

Answer 54

Fused digits | Failure of apoptosis

Question 55

What is polydactyly and what is it caused by?

Answer 55

Extra digits | Inappropriate or ectopic Shh expression

Question 56

What is ectrodactyly and what is it caused by?

Answer 56

Split hand or foot Aka lobster claw deformity Failure of the middle AER to form properly - still forms either side of the middle so end up with a split hand or foot