Embryology

Question 1

When does limb development occur?

Answer 1

Begins near the end of the 4th week

Question 2

When do the upper limb buds appear?

Answer 2

Day 24

Question 3

When do the lower limb buds appear?

Answer 3

Day 25/26

Question 4

What causes the start of limb bud development?

Answer 4

Activation of mesenchymal cells in the somatic lateral mesoderm

Question 5

What is responsible for proximo-distal patterning?

Answer 5

HOX genes

Question 6

What do HOX genes do?

Answer 6

-They are regionally expressed in limbs and determine which skeletal element is formed

Question 7

What does HOX gene expression result from?

Answer 7

A combination of the expression of SHH, FGFs and WNT7a

Question 8

What HOX genes have expression in the upper limb?

Answer 8

9-13

Question 9

What happens if you remove HOXa 11 and HOXd 11?

Answer 9

radius and ulna do not form

Question 10

How do limb buds elongate?

Answer 10

By proliferation of mesenchyme

Question 11

What do upper limb buds form opposite?

Answer 11

The caudal cervical segments

Question 12

What do lower limb buds form opposite?

Answer 12

The lumbar and sacral segments

Question 13

What happens at the apex of each limb bud?

Answer 13

The ectoderm thickens to form an apical ectodermal ridge (AER)

Question 14

Where is AER restricted to?

Answer 14

End of limb bud

Question 15

What is the structure of AER?

Answer 15

Multi-layered epithelial structure

Question 16

What impact does AER have on the limb mesenchyme?

Answer 16

Exerts an inductive influence

Question 17

What does the mesenchyme adjacent to the AER consist of?

Answer 17

Undifferentiated rapidly proliferating cells

Question 18

What happens to mesenchymal cells proximal to the AER?

Answer 18

Differentiate into blood vessels and cartilage bone models

Question 19

What happens to the distal ends of the limb buds?

Answer 19

Flatten into paddle-like hand plates and flipper-like foot plates

Question 20

What should have happened by the end of the 6th week?

Answer 20

Mesenchymal tissue in hand plates should have condensed to form digital rays

Question 21

What happens during the 7th week?

Answer 21

Digital rays are formed in the foot plates

Question 22

What is responsible for the tissue breakdown in the interdigital regions?

Answer 22

Programmed cell death (apoptosis)

Question 23

What is the apoptosis of the interdigital regions mediated by?

Answer 23

Bone morphogenetic proteins

Question 24

What happens to cartilaginous precursors in the mesoderm during the 6th week?

Answer 24

They develop by chondrification

Question 25

When do primary ossification centres appear?

Answer 25

Weeks 8-12 in response to growth factors

Question 26

What is the only limb bone that does not undergo endochondrial ossification?

Answer 26

Clavicle (membranous)

Question 27

Describe the limb rotation which takes place.

Answer 27

- Upper limbs and lower limbs rotate - Upper limbs rotate 90 degrees laterally so that extensors are on the lateral and posterior surfaces (and the thumb is lateral) - Lower limbs rotate 90 degrees medially so that the extensors are on the anterior surface (and the big toe is medial)

Question 28

How are dermatomal patterns established?

Answer 28

During the 5th week, peripheral nerves grow from the developing limb plexus (brachial and lumbosacral) into the mesenchyme of the limbs

Question 29

What are limb defects often associated with?

Answer 29

Other defects either hereditary or teratogen caused

Question 30

Amelia

Answer 30

Total absence of a limb

Question 31

Meromelia

Answer 31

Partial absence of a limb

Question 32

Phocomelia

Answer 32

Some long bones absent

Question 33

Micromelia

Answer 33

All parts present but small

Question 34

What is the critical period of limb development?

Answer 34

24-36 days

Question 35

How can lobster claw foot be inherited?

Answer 35

Autosomal dominant trait

Question 36

Polydactyly

Answer 36

- Presence of more than 5 digits on the hands and feet | - Extra digits are incompletely formed and lack muscular development

Question 37

How can polydactyly occur

Answer 37

May be inherited or teratogen induced

Question 38

Syndactyly

Answer 38

- Common birth defect of the hand or foot | - Occurs more frequent in the foot than hand

Question 39

Cutaneous syndactyly

Answer 39

Simple webbing between the digits

Question 40

Osseous syndactyly

Answer 40

Fusion of bones which occurs when notches between digital rays fail to develop

Question 41

What is thalidomide?

Answer 41

-A drug used as a sleeping tablet and anti-nausea between 1957 and 1962

Question 42

What did thalidomide use result in?

Answer 42

-Absence or deformity of long bones (intestinal atresia and cardiac abnormalities

Question 43

What is the sensitive period for thalidomide?

Answer 43

4-8 weeks

Question 44

How does thalidomide work?

Answer 44

Acts by disrupting cell adhesion and angiogenesis

Question 45

What is thalidomide now used for?

Answer 45

- Cancer - Leprosy - AIDs

Question 46

What is another name for congenital clubfoot?

Answer 46

Talipes equinovarus

Question 47

How does club foot present?

Answer 47

- Relatively common | - Sole of foot is turned medially and the foot is inverted

Question 48

What is the cause of clubfoot?

Answer 48

- Multifactorial (genetic and environmental factors) | - Abnormal positioning or restricted movement of the foetus’s lower limb in the utero (evidence is inconclusive)

Question 49

What are the 2 components of hip dysplasia?

Answer 49

- Abnormal development of the acetabulum | - Generalised joint laxity

Question 50

What causes abnormal development of the acetabulum?

Answer 50

- Common after breech births | - Breech posture during late pregnancy (abnormal development o f acetabulum and head of femur)

Question 51

What causes generalised joint laxity?

Answer 51

- Multifactorial | - Associated with congenital dislocation of the hip