Embryology

Question 1

When does limb development occur?

Answer 1

Weeks 4-8

First appear at week 4

Question 2

Where do the limb buds appear initially?

Answer 2

Venterolateral wall (outpouchings)

Question 3

Which limbs develop first?

Answer 3

Upper limbs (few days)

Question 4

Which 2 germ layers contribute to limb development?

Answer 4

• Ectoderm

- Mesoderm

Question 5

Where is the initial core tissue from?

Answer 5

Lat plate mesoderm (covered by ectoderm)

Question 6

What does the lateral plate mesoderm differentiate into?

Answer 6

Condenses to mesenchyme, which forms bones and connective tissue.

Question 7

Which part of the mesoderm is the skeletal muscle of the limbs derived from?

Answer 7

Paraxial mesoderm

Question 8

What does paraxial mesoderm divide into, and where does this take place?

Answer 8

Somites, either side of neural tube

Question 9

Which 2 parts do the somites divide into?

Answer 9

Ventral and dorsolateral

Question 10

What is the ventral part called and what does it form?

Answer 10

Sclerotome, and forms vertebral collumn

Question 11

What is the dorsolateral part called and what does it form?

Answer 11

Dermomyotome, which divides into dermatome (dermis of skin) and myotome (skeletal muscle)

Question 12

What does the myotome differentiate into?

Answer 12

• Dorsal epimere

- Ventral hypomere

Question 13

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

Answer 13

Back muscles, which are innervated by dorsal rami of spinal nerves

Question 14

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

Answer 14

Muscles of thorax, abdomen and limbs, which are innervated by ventral rami of spinal nerve

Question 15

When does the myotome differentiate into the epimere and hypomere?

Answer 15

5 weeks

Question 16

Which part of the myotome forms the limb muscles?

Answer 16

Ventral hypomere

Question 17

At which vertebral level does upper limb skeletal muscles develop from hypomere?

Answer 17

C5-C8

Question 18

At which vertebral level does lower limb skeletal muscles develop from hypomere?

Answer 18

L3-L5

Question 19

What do hypomeres divide into in the limbs? When does this occur?

Answer 19

Posterior and anterior condensations

-7 weeks

Question 20

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

Answer 20

Posterior - Extensors and supinators

Anterior - Flexors and pronators

Question 21

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

Answer 21

Posterior - Extensors and abductors

Anterior - Flexors and adductors

Question 22

What innervates the lower limb?

Answer 22

Lumbosacral plexus (L4-S3)

Question 23

When does limb rotation occur?

Answer 23

6th-8th week

Question 24

Which way does the upper limb rotate?

Answer 24

90* laterally

flexors ant

Question 25

Which way does the lower limb rotate?

Answer 25

90* medially | flexors post

Question 26

What are the 3 axes of limb rotation?

Answer 26

- PROXIMODISTAL (outwards eg shoulder >hand) - CRANIOCAUDAL (eg thumb > most cranial) - DORSOVENTRAL (palm is ventral, knuckles are dorsal)

Question 27

What growth factor is secreted by the lateral plate mesoderm?

Answer 27

Fibroblastic growth factor 10 (Fgf 10)

Question 28

What does Fgf 10 cause?

Answer 28

Thickens overlying ectoderm at tip to form apical ectodermal ridge (AER)

Question 29

What does the AER secrete?

Answer 29

Fgf 4 & 8 | NB. excess implanted into embryo > extra limbs

Question 30

What do Fgf 4 & 8 cause?

Answer 30

Rapid proliferation of mesenchymal cells underlying the AER - PROGRESS ZONE (maintains proximodistal outgrowth).

Question 31

3 growth factors involved in proximodistal outgrowth

Answer 31

``` Fgf 10 (lat plate mesoderm) Fgf 4 (AER) Fgf 8 (AER) ```

Question 32

How is dorsoventral patterning controlled?

Answer 32

Dorsal ectoderm expressed Wnt7 --> nails. | Ventral ectoderm expresses Engrailed 1 --> Wnt 7 inhibition and palm devlopment

Question 33

What does Wnt 7 expression lead to?

Answer 33

Nail formation

Question 34

What does Engrailed 1 expression lead to?

Answer 34

Wnt 7 inhibition and palm formation

Question 35

Which region of the mesenchyme controls craniocaudal development?

Answer 35

Zone of polarising activity (ZPA).

Question 36

What protein is expressed by ZPA?

Answer 36

Sonic hedgehog (Shh)

Question 37

How does Shh control limb development?

Answer 37

Shh diffuses in the cranial direction, so concentraion decreases (^ conc caudally). High concentrations induce formation of caudal structures (eg little finger)

Question 38

When do terminal limb regions flatten to form hand/foot plates?

Answer 38

Week 6

Question 39

How are fingers/toes formed from flattened plates?

Answer 39

Apoptosis - splits AER into 5 parts.

Question 40

What is amelia and what causes it?

Answer 40

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

Question 41

What is meromelia and what causes it?

Answer 41

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

Question 42

What is phocomelia and what causes it?

Answer 42

Proximal elements of the limbs are absent; normal digits, shortened limbs. -genetic factors,teratogens (eg. thalidomide)

Question 43

How does thalidomide lead to shortened limbs?

Answer 43

Inhibits Fgf 10 and Fgf 8

Question 44

What is syndactyl and what causes it?

Answer 44

Fused digits | -apoptosis failure

Question 45

What is polydactyl and what causes it?

Answer 45

Extra digits | -inappropriate Shh expression

Question 46

What is ectrodactyl and what causes it?

Answer 46

Split hand/foot | -failure of middle AER to form properly