Embryology

Question 1

When does development of the limbs start?

Answer 1

Near end of week 4

Question 2

Describe early stages of limb development

Answer 2

Activation of mesenchymal cells in somatic lateral mesoderm

Homeobox genes regulate patterning

Day 24; upper limb bud appears, 1 to 2 days later; lower limb bud appears

Question 3

Describe proximo-distal patterning

Answer 3

Regionally expressed in limbs, determine which skeletal element formed

HOX gene expression results from a combination of expression of SHH, FGF’s and WNT-7a

Question 4

What HOX genes are expressed in the upper limb?

Answer 4

HOXd 9-13

If remove HOXa 11 and HOXd 11 radius and ulna do not form

Question 5

How do limb buds form?

Answer 5

Elongate by proliferation of mesenchyme

Upper limb buds develop opposite caudal cervical segments

Lower limb buds form opposite lumbar and sacral segments

At the apex of each bud the ectoderm thickens to form an apical ectodermal ridge (AER)

Question 6

What is the AER (embryological)?

Answer 6

Apical Ectodermal Ridge

Restricted to end of limb bud and is multilayered epithelial structure

Exerts an inductive influence on limb mesenchyme

Mesenchyme adjacent to AER consists of undifferentiated, rapidly proliferating cells

Proximal mesenchymal cells differentiate into blood vessels and cartilage bone models

Question 7

How do hand and foot plates form?

Answer 7

Distal ends of limb buds flatten into paddle like hand plates and flipper like foot plates

By end 6th week mesenchymal tissue in hand plates condensed to form digital rays

During week 7 digital rays are formed in foot plates

Question 8

What is responsible for tissue breakdown in interdigital regions during development?

Answer 8

Apoptosis controls this

It is mediated by bone morphogenetic proteins

Question 9

When do hands and feet develop?

Answer 9

Between 4th and 8th weeks

Question 10

What are the final stages of limb development?

Answer 10

Cartilaginous precursors of bones develop by chondrification within mesoderm in 6th week

Primary centres of ossification appear in weeks 8-12 in response to growth factors

Endochondrial ossification for all limb bones except clavicle

Question 11

Describe limb rotation during embryological development

Answer 11

Upper and lower limbs rotate

Upper limbs rotate 90 degrees laterally so that extensors on lateral and posterior surfaces (and thumb lateral)

Lower limbs rotate 90 degrees medially so that extensors on anterior surface (and big toe medial)

Question 12

How do the dermatomal patterns develop in the limbs?

Answer 12

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

Question 13

What is amelia?

Answer 13

Total absence of a limb

Question 14

What is meromelia?

Answer 14

Partial absence of a limb

Question 15

What is phocomelia?

Answer 15

Some long bone absence

Question 16

What is micromelia?

Answer 16

All limbs present but small

Question 17

How is lobster claw foot inherited?

Answer 17

Autosomal dominant

Question 18

When is the critical period of limb development?

Answer 18

24-36 days after fertilisation

Question 19

Describe polydactyly

Answer 19

Presence of more than 5 digits on hands or feet

Extra digit incompletely formed and lacks muscular development

May be inherited or teratogen induced

Question 20

Describe syndactyly

Answer 20

Common defect

Cutaneous syndactyly (webbing between digits) is common

More frequent in foot than hand

Osseous syndactyly (fusion of bones) occurs when notches between digital rays fail to develop

Question 21

What are the birth defects caused by thalidomide?

Answer 21

Absence or deformity of long bones (intestinal atresia and cardiac anomalies)

‘sensitive’ period 4-8 weeks

Acts by disrupting cell adhesion and angiogenesis

Question 22

Describe congenital clubfoot

Answer 22

aka talipes equinovarus

relatively common; idiopathic most common

Sole of foot turned medially and foot inverted

Causes;

• multifactorial (genetic and environmental)
• ? abnormal positioning or restricted movement of fetus’ lower limb in utero

Question 23

Describe developmental dysplasia of hip

Answer 23

Abnormal development of acetabulum

15% infants w/ congenital dislocation

Common after breech deliveries

Generalised joint laxity; multifactorial and associated with congenital dislocation of hip