Development of Limbs Flashcards
Which parts of the embryo specifically allow limb development?
The somites
The lateral plate mesoderm
What happens to the Notochord on limb formation?
It is marooned and a remnant forms - The nucleus pulpsis of the intervertebral disc.
What are the 3 degrees of asymmetry in the limb?
Proximal distal axis
Dorsal ventral asymmetry
Anterior posterior axis of asymmetry
What sequence does embryonic development occur in?
Head to tail
When do limb buds appear?
On the folded embryo. Upper limb buds first
What do the limb buds look like?
Flipper like structures.
What direction do the limb buds extend first?
Ventrally away from the trunk towards the belly.
What drives the significant elongation of the limb buds?
Cellular division
What happens before the limbs adopt their adult orientation?
Primordia of hands and feet begin to appear
What does limb bud development begin with?
Activation of mesenchyme in the somatic layer of the lateral plate mesoderm
What forms the limb buds?
Proliferation of somatopleuric lateral plate mesoderm
What are the limb buds made of?
An outer ectodermal cap
A core of mesoderm
What does the mesoderm differentiate into to allow lengthening of the limb bud?
Mesenchymal cells
What is the Apical Ectodermal Ridge?
Each limb bud forms the ectoderm along the apex of the limb bud, differentiates into a ridge like thickening (The AER)
Why is Apical Ectodermal ridge important?
It is essential for limb differentiation anf it induces this throughout the limb.
What does the Apical Ectodermal ridge express and what does this do?
FGF2, FGF4, FGF8.
They all induce limb outgrowth by maintaining proliferation in the progress zone
When does the Apical Ectodermal ridge regress?
When the limb flatterns into paddle appearance
What is the Zone of Polarising activity?
Responsible for the generation of mirror image limbs
What does the Zone of Polarising activity control?
The patterning of the limbs and maintenance of the AER
Where is the Zone of Polarising activity?
Small signalling centre found in the posterior limb bud margin
How are the hands and feet sculpted from the paddles?
There is development of a cartiaginous model of the bones and apoptosis occurs between these to sculpt.
How do the digits proliferate?
The Apical Ectodermal ridge breaks up, but stays over the tips of the digitsso these regions can still proliferate.
What does the Apical Ectodermal ridge signal to tissues?
To remain undifferentiated
How does bone ossification occur?
The Apical Ectodermal ridge regresses so the cartilage model differentiates then undergoes endochondrial ossification
Where is the primary ossification centre?
In the diaphysis
Where is the secondary ossification centre?
In the epiphyses (Allows growth up to puberty)
How does migration of myogenic precursers bring specific innervation with it?
They migrate from a somite that has its own spinal nerve so the specific innervation is brought with it during migration
How are discrete muscle bellies formed?
Development of the precursers continues and the muscle masses split.
What is the upper flexor compartment made from?
The ventral limb
What is the upper extensor compartment made from?
The dorsal limb
What is the lower extensor compartment made from?
Ventral limb
What is the lower flexor compartment made from?
Dorsal limb.
Why are the lower limb compartments opposite to the upper limb compartments?
Because the lower limb rotates during development
Why is the rotation of the lower limb important?
It allows for the mirror image orientation of the upper and lower limbs.
How is the proximal distal axis generated?
The AER exerts and inductive influence on the mesenchyme in the limb bud.
As the bud elongates the proximal tissue is too far from the AER
The mesenchyme differentiates
How is dorsal ventral patterning generated?
The position of the AER marks the boundary between dorsal and central limb ectoderm. Both will release signals to induce relative differentiation
How is the anterior posterior axis generated?
The ZPA secretes morphogen that diffuses into the tissue and creates a concentration gradient as it is broken down.
What does pre axial refer to?
The thumb and big toe
What does post axial refer to?
The little finger and toe side of the limb
What is the significance of the pre and post axial ventral lines?
They represent a border in the limb where there is no overlap of dermatomes
Which axial specification does the AER control?
Proximal distal asymmetry
Dorsal and ventral axis boundary
Which axial specification does the ZPA control?
Maintains the AER
Anterior to posterior asymmetry
Why is the upper limb effected more often by limb defects, compared to the lower limb?
Because of the lag period between their development.
What are the common limb defects?
Syndactyly Polydactyly Amelia Meromelia Phocomelia
What is Syndactyly?
Fusion of the digits (can be skin or skin and bones)
What is Polydactyly?
Extra digits
Genetic recessive
What is Amelia?
Complete absence of a limb
Could be due to failure of the AER
What is Meromelia?
Partial absence of one or more limb structures
What is Phocomelia?
Varient of Meromelia where all of the long bones of the limbs are absent.
Clinically, what is a dermatome?
A strip of skin that can be examined and is innervated by a single spinal nerve
What is a myotome?
A muscle or group of muscles which are innervated by a single spinal nerve
