Movement lecture 1: Limb development Flashcards
When does limb development take place?
Mid-late embryonic phase, weeks 4-8.
What is visible at the end of week 4?
Limb buds are visible as outpouchings from the ventrolateral body wall.
What does core limb bud tissue consist of?
Derived from lateral plate mesoderm covered by a layer of ectoderm.
What does the limb bud mesoderm core differentiate into?
Mesenchyme
What will the mesenchyme form?
Bones and connective tissue.
What germ layer is the skeletal muscle of the limbs derived from?
Paraxial mesoderm.
What happens to the paraxial mesoderm either side of the neural tube and how is this relevant to limb development?
Develops into somites. These will migrate into limb buds and form skeletal muscle.
Describe somite differetiation in the limb buds.
- Divide into a ventral part called the sclerotome, which forms the vertebral column.
- The dorsolateral part forms a dermomyotome which divides into a dermatome and a myotome.
- The dermatome gives rise to the dermis of the skin and the myotome gives rise to skeletal muscles.
What two components does the myotome differentiate into?
Dorsal epimere and ventral hypomere.
What develops from the epimere?
Back muscles which are innervated by the dorsal rami of spinal nerves.
What develops from the hypomere?
Muscles of thoracic and abdominal walls and muscles of limbs which are innervated by the ventral rami of spinal nerves.
Does limb skeletal muscle form from hypomere or epimere?
Hypomere - region adjacent to the level of the developing upper (C5-8) and lower (L3-5) limb buds.
How is the hypomere divided?
Into the posterior and anterior condensation.
Which muscles are derived from the posterior condesation?
Extensors and supinators of the upper limbs.
Extensors and abductors of lower limbs.
What is the origin of the nerve supply to the limbs?
Ventral primary rami.
What is the origin of the nerve supply to the upper limb?
Brachial plexus C5-T1
What is the origin of the nerve supply to the lower limb?
Lumbosacral plexus
Why do anterior and posterior compartments of limbs have different nerve supplies?
Each spinal nerve migrates into the limb bud with the developing musculature as anterior and posterior branches.
Between what weeks does limb rotation occur?
6-8
Describe the rotation of the upper limbs.
Upper limbs rotate 90° laterally so flexors lie anteriorly.
Describe the rotation of the lower limbs.
Lower limbs rotate 90° medially so flexors lie posteriorly.
What are the axes of the limb?
Proximodistal – from the shoulder/hip to the hand/foot
Craniocaudal – the thumb is most cranial digit and the little finger is most caudal
Dorsoventral – the palm of the hand and sole of the foot are ventral and the knuckle side of the hand/foot are dorsal
What is secreted by the lateral plate mesoderm forming the mesenchymal core of the limb bud?
Fibroblast growth factor (Fgf 10).
What is the function of the apical ectodermal ridge?
Expresses fibroblastic growth factors -Fgf 4 and 8. These cause rapid proliferation of mesenchymal cells underlying the AER – the progress zone. The progress zone maintains proximodistal outgrowth of the limb.
What is the effect of early removal of the AER?
The limb is extremely forshortened.
What is the effect of late removal of the AER?
The limb is partially forshortened.
What is the effect of implanting Fgf-soaked beads?
Supernumerary limbs at the site of implantation.
How is dorsoventral patterning controlled?
The dorsal ectoderm expresses Wnt7 whereas the ventral ectoderm expresses Engrailed-1 which inhibits Wnt7
What happens to Wnt7 knockout mice?
They develop foot pads on the dorsal and ventral surface.
How is the craniocaudal axis determined?
The craniocaudal axis is determined by a small region of mesenchyme in the caudal part of the limb bud – the zone of polarising activity (ZPA) - where sonic hedgehog (Shh) is expressed.
Shh diffuses from the ZPA in a cranial direction.
How does sonic hedgehog protein work?
High concentration of Shh induces formation of caudal structures e.g. little finger whereas low concentration induces formation of cranial structures e.g. thumb.
How are digits formed?
Fingers and toes are formed by programmed cell death (apoptosis) in the AER. This splits the AER into 5 parts which continue to grow to form fingers.
Define amelia.
Complete absence of a limb e.g. early loss of Fgf signalling.
Define meromelia.
Partial absence of a limb e.g. later or partial loss of Fgf signalling.
Define phocomelia
Digits develop prematurely. Proximal elements of limb absent e.g. flipper limb. Can be due to genetic factors or teratogen e.g. Thalidomide inhibits Fgf 10 and 8 expression.
Define syndactyly.
Fused digits. Failure of apoptosis.
Define polydactyly.
Extra digits. inappropriate/ectopic shh expression.
