Limb development Flashcards
Tetrapod limb is created as 3 segments. List them & state what they form…
- Stylopod (proximal) - humerus & femur
- Zeugopod - radius, ulna/tib, fib
- Autopod (distal) - carpals/tarsals
- Understand the inductive processes involved in limb bud development and limb outgrowth and state the factors involved. You will also be able to identify which structures are specified within the different limb regions.
- Understand the role of the AER and ZPA in establishment of limb polarity, know the molecules involved in these processes and what goes wrong when these signalling centres are perturbed.
- Be familiar with the processes involved in digit specification and separation and how this occurs.
- Understand the importance of appropriate control of postnatal bone growth.
…
How are limb buds formed?
mesenchymal condensation of lateral paraxial mesoderm
What are the limb-inducing signals?
Lateral plate mesoderm destined to become limb skeleton
- paracrine factor FGF10 -> initiates limb bud formation
- Formation of the Apical Ectodermal Ridge (AER - important)
T or F - Development of the forelimb precedes that of the hindlimb
true
What is AER? Functions…? It’s a bitch but may be important!
Apical Ectodermal Ridge
- keeps the underlying mesenchyme in a ‘plastic’ proliferative state to ensure limb outgrowth – the progress zone (PZ)
- Maintains expression of molecules that specify the A/P (thumb-pinkie) axis
- Interacts with proteins that specify the D/V (knuckle- palm) axis of the distal limb
What happens when AER is ‘removed’ in development? What happens when AER is ‘duplicated’ in development?
removed -> limb dev. ceases
duplicated -> limb duplicated
Why is FGF important?
FGF is involved in initiation and maintenance of the AER
Factors involved in digit formation… factor important in forming digits?
- Increase Mesenchymal density in distal extremity
- Tissue between rays programmed to degenerate -> if no mesenchymal cell death – soft tissue web
- factor causing normal digit formation is N-Myc
After limb bud appears, digits form … days later?
4 - 10 days later
factor causing normal digit formation is…? important!
N-Myc
Define ZPA… polarising signal (gene)
The Zone of Polarizing Activity (ZPA) is an area of mesenchyme that contains signals (Shh) which instruct the developing limb bud to form along the anterior/posterior axis. Limb bud is undifferentiated mesenchyme enclosed by an ectoderm covering. Eventually, the limb bud develops into bones, tendons, muscles and joints.
Duplication of ZPA results in…? ie. overexpression of Shh
distal limb duplication - ‘polydactyly’ (many digits)

Re distal limb modification. Ancestral 5 digits is reduced in sequence. what is the sequence?
1st, 5th, 2nd, 4th
Bones of the limb are formed by…?
endochondral ossification
