Embryology Flashcards
When does development of the limbs begin?
Near the end of the 4th week of development;
- activation of mesenchymal cells in the somatic lateral mesoderm
- homeobox genes regulate patterning
When do the upper and lower limb buds appear?
Day 24 - upper limb buds appear
Lower limb buds appear 1-2 days later
Where are the HOX genes expressed and what do they determine?
Regionally expressed in the limbs
Proximo-distal patterning - determine which skeletal element is formed
What does HOX gene expression result from?
A combination of the expression of SHH, FGFs and WNT-7a
What happens if HOXa and HOXd11 are removed?
The radius and ulna do not form
How do the limb buds elongate?
By the proliferation of the mesenchyme
Where do the upper and lower limb buds develop?
Upper limb buds develop opposite the caudal cervical segments
Lower limb buds develop 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)
What are the features and functions of the apical ectodermal ridge?
AER is restricted to the end of the limb bud
Multi-layered epithelial structure
Exerts an inductive influence on the limb mesenchyme
Mesenchymal cells proximal to the AER differentiate into blood vessels, cartilage and bone models
What does the mesenchyme adjacent to the AER consist of?
Undifferentiated, rapidly proliferating cells
How do the hand and foot plates develop?
The distal ends of the limb buds flatten into paddle-like hand plates and flipper-like foot plates
By the end of the 6th week, mesenchymal tissue in the hand plates is condensed to form digital rays
During the 7th week, digital rays are formed in the foot plates
When do the hands and feet develop?
Between 4th and 8th weeks
What is responsible for the tissue breakdown in the inter-digital regions, and what is this mediated by?
Apoptosis is responsible for the tissue breakdown
This is mediated by bone morphogenetic proteins
What are the final stages of limb development?
Cartilaginous precursors of the limb bones develop by chondrification within the mesoderm in the 6th week
Primary centres of ossification appear in weeks 8 to 12 in response to growth factors
Endochondrial ossification occurs for all limb bones except the clavicle
How far do the 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 extensors are on the anterior surface, and the big toe is medial
When do peripheral nerves grow from the developing limb plexus into the mesenchyme of the limbs?
During the 5th week
What are birth defects of the limbs often associated with?
Other defects
Hereditary abnormality
Teratogen exposure
What is the term for the total absence of the limbs?
Amelia
What is the term for partial absences of the limbs?
Meromelia
What is the term for some long bone absence?
Phocomelia
What is the term used when all limb parts are present but are small?
Micromelia
When is the critical period of limb development?
24-36 days after fertilisation
What is polydactyly?
Presence of more than 5 digits on the hands or feet
Extra digit is completely formed and lacks muscular development
May be inherited or teratogen induced
What is syndactyly?
Common birth defect of the hand or foot
Cutaneous syndactyly is where there is webbing between the digits, common limb defect and more common in foot than in hand
Osseous syndactyly occurs where notches between the digital rays fail to develop
What birth defects were caused by thalidomide?
Caused absence or deformity of long bones
Acted by disrupting cell adhesion and angiogenesis
What is talipes equinovarus?
Congenital club foot
Sole of the foot is turned medially and the foot is inverted
What are the causes of talipes equinovarus?
Multifactorial - genetic and environmental
Possibly due to abnormal positioning or restricted movement of the foetus’s lower limb in utero
What percentage of infants with congenital dislocation of the hip will have developmental dysplasia of the hip?
15%
When is developmental dysplasia of the hip common?
After breech deliveries - breech posture during late pregnancy may cause abnormal development of acetabulum and head of femur
What are the causes of developmental dysplasia of the hip?
Multifactorial
Generalised joint laxity
Associated with congenital dislocation of the hip
