Development Of Limbs Flashcards
When do the limb buds appear?
Towards the end of the 4th week
Do the lower and upper limbs develop simultaneously?
Lower limb development lags (by 2 days)
What is a limb bud?
Core of proliferating mesenchymal cells with an ectoderm covering that emerge from the trunk of the embryo
How does the limb bud elongate?
Proliferation of mesenchymal core
What is the AER?
Apical ectodermal ridge (thickened ectoderm at the apex of the limb?
What are the 3 spatial axes in limb development?
- Shoulder to fingertips
Proximal – distal axis - Palmar surface to dorsal surface
Dorsal – ventral axis - Side – to – side
Anterior – posterior axis
What controls the anterior to posterior axis?
Zone of polarising activity (ZPA)
What controls the proximal to distal axis?
Apical ectodermal ridge (AER)
What controls the dorsal to ventral axis?
Ectoderm
Describe the importance of the apical ectodermal ridge
- Critical for limb bud outgrowth - cells in the ridge are different
- Orchestrates limb development proximal to distal
- Final stage is appearance of paddles (as they flatten)
- Then AER regresses
How does the AER orchestrate limb development?
- AER releases signals to tell mesenchyme to remain undifferentiated
- Signals are diffusion limited
- Proximal mesenchyme begins to differentiate into constituent tissues
- Finally, induces development of digits
What is the ZPA?
Zone of polarising activity = signalling centre located at the posterior base of the limb bud that contributes to the generation of asymmetry in the limbs
What are digital rays?
Mesenchyme condensations within plates that are cartilaginous models of the digital bones
How are the digits in the hand and foot formed?
- AER breaks up and its only maintained over the tips of the digital rays
- Interdigital spaces are sculpted by apoptosis
What is syndactyly
Fusion of the digits, may involve just CT (e.g. Rosebud hand) or bones may be fused
What is polydactyly?
Extra digits, genetic recessive trait
What is Amelia?
Complete absence of a limb
What is meromelia?
Partial absence of one or more limbs
What is phocomelia?
Hand and feet are attached directly to the trunk
What causes malformation?
Intrinsic error in coordination of morphogenesis i.e. Something wrong in the signalling mechanisms due to mutation error
What is amniotic band constriction?
Congenital disorder caused by entrapment of normally formed foetal parts caused by fibrous amniotic bands while in utero (constriction bands). Leads to deformation.
How does thalidomide disrupt morphogenesis?
Disrupts the AER, stops the elongation of limb buds
Which external agents can disrupt morphogenesis?
E.g. Thalidomide and TORCH infections
TORCH, which includes Toxoplasmosis, Other (syphilis, varicella-zoster, parvovirus B19), Rubella, Cytomegalovirus (CMV), and Herpes infections, are some of the most common infections associated with congenital anomalies.
How do the limb buds become innervated?
- Upper limb bud appears opposite the caudal cervical spinal segments
- Lower limb opposite lumbar & sacral spinal segments
- Spinal nerves enter the limb bud early in its development
How do bones and muscle form in the newly developed limb buds?
- Mesenchymal differentiation creates a cartilage model
- Myogenic precursors migrate into limbs from somites
- Come together to form two common muscle masses around the newly formed skeletal elements
1. Ventral = flexor
2. Dorsal = extensor - Individual muscles then split from common masses
How do the limbs rotate?
• Limbs extend ventrally at first • But, as they elongate, they rotate • Upper limb: laterally – thumb lateral • Lower limb: medially – big toe medial
Describe the position of the embryo before and after limb rotation
Before
- thumbs up
- elbows out
- soles facing
- knees out
After
- thumbs out
- elbows down
- soles down
- knees up
