Embryology Flashcards
When does limb development occur?
Begins near the end of the 4th week
When do the upper limb buds appear?
Day 24
When do the lower limb buds appear?
Day 25/26
What causes the start of limb bud development?
Activation of mesenchymal cells in the somatic lateral mesoderm
What is responsible for proximo-distal patterning?
HOX genes
What do HOX genes do?
-They are regionally expressed in limbs and determine which skeletal element is formed
What does HOX gene expression result from?
A combination of the expression of SHH, FGFs and WNT7a
What HOX genes have expression in the upper limb?
9-13
What happens if you remove HOXa 11 and HOXd 11?
radius and ulna do not form
How do limb buds elongate?
By proliferation of mesenchyme
What do upper limb buds form opposite?
The caudal cervical segments
What do lower limb buds form opposite?
The lumbar and sacral segments
What happens at the apex of each limb bud?
The ectoderm thickens to form an apical ectodermal ridge (AER)
Where is AER restricted to?
End of limb bud
What is the structure of AER?
Multi-layered epithelial structure
What impact does AER have on the limb mesenchyme?
Exerts an inductive influence
What does the mesenchyme adjacent to the AER consist of?
Undifferentiated rapidly proliferating cells
What happens to mesenchymal cells proximal to the AER?
Differentiate into blood vessels and cartilage bone models
What happens to the distal ends of the limb buds?
Flatten into paddle-like hand plates and flipper-like foot plates
What should have happened by the end of the 6th week?
Mesenchymal tissue in hand plates should have condensed to form digital rays
What happens during the 7th week?
Digital rays are formed in the foot plates
What is responsible for the tissue breakdown in the interdigital regions?
Programmed cell death (apoptosis)
What is the apoptosis of the interdigital regions mediated by?
Bone morphogenetic proteins
What happens to cartilaginous precursors in the mesoderm during the 6th week?
They develop by chondrification
When do primary ossification centres appear?
Weeks 8-12 in response to growth factors
What is the only limb bone that does not undergo endochondrial ossification?
Clavicle (membranous)
Describe the limb rotation which takes place.
- Upper limbs and lower limbs rotate
- Upper limbs rotate 90 degrees laterally so that extensors are on the lateral and posterior surfaces (and the thumb is lateral)
- Lower limbs rotate 90 degrees medially so that the extensors are on the anterior surface (and the big toe is medial)
How are dermatomal patterns established?
During the 5th week, peripheral nerves grow from the developing limb plexus
(brachial and lumbosacral) into the mesenchyme of the limbs
What are limb defects often associated with?
Other defects either hereditary or teratogen caused
Amelia
Total absence of a limb
Meromelia
Partial absence of a limb
Phocomelia
Some long bones absent
Micromelia
All parts present but small
What is the critical period of limb development?
24-36 days
How can lobster claw foot be inherited?
Autosomal dominant trait
Polydactyly
- Presence of more than 5 digits on the hands and feet
- Extra digits are incompletely formed and lack muscular development
How can polydactyly occur
May be inherited or teratogen induced
Syndactyly
- Common birth defect of the hand or foot
- Occurs more frequent in the foot than hand
Cutaneous syndactyly
Simple webbing between the digits
Osseous syndactyly
Fusion of bones which occurs when notches between digital rays fail to develop
What is thalidomide?
-A drug used as a sleeping tablet and anti-nausea between 1957 and 1962
What did thalidomide use result in?
-Absence or deformity of long bones (intestinal atresia and cardiac abnormalities
What is the sensitive period for thalidomide?
4-8 weeks
How does thalidomide work?
Acts by disrupting cell adhesion and angiogenesis
What is thalidomide now used for?
- Cancer
- Leprosy
- AIDs
What is another name for congenital clubfoot?
Talipes equinovarus
How does club foot present?
- Relatively common
- Sole of foot is turned medially and the foot is inverted
What is the cause of clubfoot?
- Multifactorial (genetic and environmental factors)
- Abnormal positioning or restricted movement of the foetus’s lower limb in the utero (evidence is inconclusive)
What are the 2 components of hip dysplasia?
- Abnormal development of the acetabulum
- Generalised joint laxity
What causes abnormal development of the acetabulum?
- Common after breech births
- Breech posture during late pregnancy (abnormal development o f acetabulum and head of femur)
What causes generalised joint laxity?
- Multifactorial
- Associated with congenital dislocation of the hip
