Development of the Limbs Flashcards
What does limb development begin with?
The activation of mesenchyme within the somatic layer of lateral mesoderm
What does the somatic mesoderm form?
The limb skeleton
What do somites form?
The limb musculature
When do limb buds appear?
Towards the end of week 4
How does development of the lower limbs differ from that of the upper limbs?
It lags about two days behind
Where do limb buds appear?
On the ventero-lateral body wall
What happens to limb buds first?
They extend ventrally
What do limb buds consist of?
A mesenchyme core with a thickened ectoderm at the apex, the apical ectodermal ridge (AER)
What is mesenchyme?
Flexible mesoderm
How does elongation of the limb bud occur?
Through proliferation of the mesenchyme core
What is the apical ectodermal ridge critical for?
Limb bud outgrowth
What does the AER orchestrate?
Limb development proximal to distal
What is the effect of AER on the mesenchyme immediately underlying it?
It keeps it undifferentiated
What happens to undifferentiated mesenchyme in the limb buds?
It proliferates, leading to elongation
What happens to proximal mesenchyme?
It begins to differentiate into its constituent tissues as it is too far away from the AER to receive the signals to stay undifferentiated
What does the AER eventually do?
Induces the development of the digits within the hand/foot plates and regresses
What is the zone of polarising activity (ZPA)?
A signally centre
Where is the ZPA located?
At the posterior base of the limb bud
What is the ZPA responsible for?
Generation of asymmetry in the limbs
Controls patterning
Maintains the AER
What does the AER mark?
The boundary between dorsal and ventral limb ectoderm
How does dorsoventral patterning occur?
The ectoderm exerts dorsalising and centralising influences over the mesenchyme core
What controls the anterior-posterior specification in development of the limbs?
ZPA
What controls the proximal-distal specification in development of the limbs?
AER
What controls dorsal-ventral specification in development of the limbs?
Ectoderm
What are digital rays?
Mesenchyme condensations within plates forming cartilaginous models of the digital bones
What happens to the AER in digital rays?
It breaks up, and is maintained only over the tips of the digital rays
What happens to the interdigital spaces of the digital rays?
They are progressively sculpted by apoptosis
What are the stages in the formation of bones?
Signals from the AER to remain undifferentiated stop
Lateral plate mesoderm condenses and differentiates
Cartilage model forms
Endocondral ossification
Primary and secondary ossification centres form
How are muscles formed in the limbs?
Myogenic precursors migrate into the limbs from the somites and coalesce into two common muscle masses around the newly formed skeletal elements
What are the two common muscle masses in the developing limb?
Ventral
Dorsal
What does the ventral muscle mass in the developing limb form?
Flexors
What does the dorsal muscle mass in the developing limb form?
Extensors
What happens to the common muscle masses in the developing limbs?
Individual muscles split from the common masses
How do the extensor and flexor compartments differ in the upper and lower limb?
They are on opposite sides
What happens as the limbs extend ventrally?
They rotate
In what direction does the upper limb rotate as it extends?
Laterally- thumb is lateral
In what direction does the lower limb rotate as it extends?
Medially- big toe is medial
Where does the upper limb bud appear?
Opposite the caudal cervical spinal segments
Where does the lower limb bud appear?
Opposite the lumbar and sacral spinal segments
When do the spinal nerves enter the limb bud?
Early in its development
What happens if the spinal nerves don’t enter the limb bud early in its development?
Without the innervation, development stalls
What happens to muscles in the developing limb?
They are compartmentalised
What happens to the compartments of muscles in the developing limb?
Nerves grow into common muscle masses
What happens to the anterior divisions of nerves for the anterior (ventral) compartment of muscles?
They regroup to form medial and lateral cords of the brachial plexus, and therefore medial and lateral cords supply flexors
What happens to the posterior divisions of nerves for the posterior (dorsal) compartment of muscles?
They regroup to form the posterior cord, therefore the posterior cord branches supply extensors
What do nails develop from?
Nail fields on the tips of the fingers
How do nail fields get to where they need to be?
They migrate onto the dorsal surface, bringing their nerve supply with them
What is a dermatome?
Strip of skin supplied by single spinal nerve
What is a myotome?
Muscle/group of muscles supplied by a single spinal nerve
What is more commonly affected by limb defects, upper or lower?
Upper limb
Why is the incidence of upper and lower limb defects different?
Because the lag period of two days mean they have different critical periods
What is the incidence of limb defects?
6 in 10,000 live births
What causes limb defects?
Usually hereditary
Teratogen defects have been described
What are the common limb defects?
Amelia
Meromelia
What is amelia?
Complete absence of a limb
What is meromelia?
Partial absence of one or more limb structures
Give an example of meromelia
Phocomelia (phalidomide)
What are the digit defects?
Syndactole
Polydactyl
What is syndactole?
Digits fused
What causes syndactole?
Lack of apoptosis between digits
What is polydactlyl?
Too many digits
