L8: Development of the Limbs Flashcards
When does limb development start?
Week 5
What does the mesoderm differentiate into?
The mesoderm forms somites in differentiation. Somites are very close to the notochord. We develop lateral plate mesoderm which lies laterally to the somites. The region of the neuroplate thickens and forming the neural tube and the notochord remains below it. We also get folding of the trilaminar disc getting a tube structure.
What does the myotome differentiate into?
Skeletal msucles -
The myotome is the more ventral part of the dermatomyotome. The ventral part of the myotome goes onto form the muscle of the limbs and contributes to muscles of the thoracic abdominal wall. Innervated by the ventral rami of spinal nerves – just as the brachial plexus also innervated by the ventral rami. The dorsal part becomes the muscles of the pack innervated by the dorsal rami. The dermatome will go onto form the dermis of the skin.
What do the somites divide into?
In the folding of the trilaminar disc the somites differentiate into a dermatomyotome: dermatome (dorsolarteral) and myotome. The sclerotome the ventral part goes onto develop into the vertebral column.
When do the limb buds appear?
he limb buds are outpunches from the ventral body wall. They start to appear by week 4. The hindlimb bud lags behind forelimb bud by 4 days.
What are the limb buds composed of?
Limb buds have lateral plate inside the them. This is composed of mesoderm. The LPM core differentiates to form cartilage models first, which then ossify to form the bone. This is covered by a layer of ectoderm.
Describe somite migration into the limb buds?
The skeletal muscle comes from a migration into the limb bud from the somites. The LPM gives the connective tissue and bone tissue from the somites migrating into the limb bud give the skeletal muscle. Some migrate anteriorly to give muscles of the anterior nobody wall. Some migrate into the limb bud to give skeletal muscle.
As the tissue from the somites migrates it takes with it the growth of the nervous tissue from the ventral rami of the spinal nerve. They then grow into them. Muscles and the nerve only develop functionally together if the grow together. Issues with migration means we do not get full development of either.
What does the mesoderm in the limb buds condense into?
When the mesoderm gets into the limb buds it condenses into an anterior and a posterior part. In the upper limb the posterior part gives rise to the extensors and the same in the lower limb. The anterior condensation gives rise to flexors.
Describe limb rotation.
There is a reversal in the lower limb. The limbs rotate in different direction. The UL laterally and the LL medially. This is why the limb is on the lateral aspect and the LL the bug toe is on the medial aspect. The extensors are on the posterior aspect in the UL and anterior aspect (quads) in the LL.
Descirbe proximodistal patterning.
Proximodistal outgrowth – the tip of the developing limb bud is found the apical ectodermal ridge. It is formed by ectoderm. This develops a fibroblast growth factor to cause the development of the ridge. Once the ridge is formed it secretes fibroblast growth factors of its own (4 and 8) causing rapid proliferation of the cells underlying the AER- the progress zone. The PZ keepings maintain the cells and adds tissue.
Describe deformations that can occur due to incorrect proximodistal patterning.
Disruption of the AER disrupt proximodistal growth. If the AER is removed later, we get most of the structure of the limb forming but the terminal part not forming.
In Amelia – there is early failure of the FGF and AER.
Meromelia – shortened limbs – premature failure due to later or partial loss of FGF signalling/AER function leading to an arrest of outgrowth. Vascular abnormalities may also be responsible.
Different parts of the AER can fail. There can be partial failure e.g. thought to happen in cleft split foot or hand. The progress zone in different areas develops but the middle part doesn’t. Absence of the 2 and 3rd metacarpal but growth of the lateral and medial metacarpal.
Ectopic FGF can lead to another limb developing. The musculature in the extra limb is less well developed. The limb is flexed. This means it may have some function.
Descirbe craniocaudal patterning.
This explains why the thumb is lateral and the little finger is medial. This is determined by a region of mesenchyme in the caudal part of the limb bud – the zone of polarising activity (ZPA). The caudal part is the part that will give rise to caudal structures such as the little finger. It secretes sonic hedgehog. A high concentration in the caudal region induces caudal structures to form. SHH diffuses from the ZPA in the cranial direction. Ring, middle and index develop under progressively lower levels of SHH – each slightly different levels. This is why these digits look very similar. Low concentration cranially induces cranial structures e.g. thumb.
Describe deformations that can occur due to incorrect craniocaudal patterning.
Ectopic ZPA means SHH diffuses leading to mirror image duplications of structures. This means potentially polydactyly – mirror images.
Descirbe dorsoventral patterning.
Explains why the dorsal and ventral pattern of our limbs look different. Dorsal ectoderm express factors that encourage dorsal structures to develop. Ventral ectoderms expresses engariled-1.This inhibits dorsal structures to from.
Dorsal ectoderm expresses Wnt7 which activates LMX1. LMX1 specifies development of doral strtures. The Engrailed-1 inhibits Wnt7 so dorsal structures cannot forming allowing ventral sturtures to form.
Describe deformations that can occur due to incorrect dorsoventral patterning.
Nail patellar syndrome
Quite rare. Effects the nails, bone, kidney and the eyes. The nails are on the dorsum are poorly developed. The patellar is also missing. These are both dorsal structures.
Syndactyly
Under AER we get lengthening in the segments in the 5 segment but there is no growth in the parts in between. We do not get apoptosis between them. We then get lengthen of the hand and separation.
We still get proximal distal outgrowth but we do not get cell growth separating them, leading to fusion of the digits.