Development Of The Limb

Question 1

What are the three axes that limb bud differentiation occur on?

Answer 1

Proximal distal
Anterior posterior
Dorsal ventral

Question 2

What are Homeobox genes responsible for?

Answer 2

Specification of limb fields & regulating patterning in formation of limbs

Question 3

Which proteins regulate induction of early limb bud and activate mesenchymal cells in lateral mesoderm?

Answer 3

Wnt proteins and fibroblast growth factors

Question 4

What are the early stages of limb development?

Answer 4

Limb buds form deep to a thick band of ectoderm (Apical Ectodermal Ridge, AER) at the end of the fourth week, buds appear on ventrolateral body wall

Question 5

AER is induced by underlying mesoderm. List the two proteins responsible for this process and outline their individual roles.

Answer 5

1. Bone morphological protein - signals
2. FGFs - induction and maintenance of AWR

*wolfian duct may be important

Question 6

After being induced, what does the AER itself induce?

Answer 6

AER induces limb mesenchyme that initiates growth & development of limbs in a proximal-distal axis
FGFs in AER are responsible for this

Question 7

Outline the formation of the zone of polarising activity (ZPA) and the consequence of this formation

Answer 7

1. Mesenchymal cells aggregate at the posterior margin of the limb bud to form ZPA
2. FGF from AER activates ZPA to express Sonic hedgehog (Shh) genes. These gene secretions control patterning of the limb along the anterior-posterior axis

Question 8

What do the dorsal and ventral epidermis of the limb bud then express?

Answer 8

Wnt 7 and EN-1 respectively. These proteins are responsible in specifying the dorsal ventral axis

Question 9

Mesenchyme proximal to AER differentiates into…

Answer 9

Blood vessels and cartilage bone models

Question 10

How are handplates and footplates formed?

Answer 10

Distal ends of limb buds flatten

Question 11

At the end of week 6, mesenchymal tissue in handplates has condensed into digital rays and in week 7 mesenchymal tissue in footplates condense into digital rays and toes. What does the AER at tip of each digital ray induce?

Answer 11

Development of mesenchymal primordia of bones (phalanges) in the digits

Question 12

What processes help joint and digit formation?

Answer 12

Apoptosis and tissue breakdown in interdigital regions

Question 13

What does BMP7 do?

Answer 13

Promotes cartilage formation

Question 14

What does BMP2 do

Answer 14

It is expressed between bones to form joints

Question 15

What protein and vasculature is critical to joint formation?

Answer 15

Wnt proteins and blood vessels

Question 16

What happens between weeks 5-7 in terms of bone formation?

Answer 16

Week 5 - chondrification centres appear
End of week 6 - entire skeleton is cartilaginous
Week 7 - osteogenesis of long bones begins from primary ossification centres