Embyrology Flashcards
When does limb bud development begin and with what?
4th week with the activation of mesenchymal cells in the somatic lateral mesoderm
What is embyrological patterning?
Grouping of cells together in the proper relationship to each other and the tissue surrounding them
What genes control embryological patterning of the limbs?
Homeobox genes
At what days do the limb buds appear?
Day 24 - upper limb bud appears
Day 25-26 - lower limb bud appears
What do HOX genes do?
Control the body plan of an embryo from head to toe
Where are HOX genes expressed?
Regionally in limbs
They determine which skeletal element is formed
HOX expression results from combination of expression of what 3 other things?
SHH, FGFs, WNT-7a
What type of HOX is expressed in the upper limb?
HOX 9-13
Removal of what two HOX genes will lead to the radius and ulna not forming?
HOXa11, HOXd11
How do limb buds elongate?
By proliferation of mesenchyme (embryonic connective tissue)
Where do the upper limb and lower limb buds develop?
Upper limb - opposite caudal cervical segments
Lower limb - opposite lumbar and sacral segments
What forms at the apex of each limb bud?
Apical ectodermal ridge (AER)
What are the AER?
Multi-layered epithelial structure that is restricted to the end of limb bud
What do the AERs do?
Exert an inductive influence on limb mesenchyme
What lies adjacent to the AER?
Undifferentiated, rapidly proliferating cells
What lies proximal to the AER?
Mesenchymal cells which differentiate into Bas and cartilage bone models
What develops at the end of the limb buds?
Flattened hand plates/foot plates
By the end of the 6th week, what happens in the hand plates?
Mesenchymal tissue condenses to form digital rays
By the end of the 7th week, what happens in the foot plates?
Digital rays form
What prevents webbed fingers/toes occurring?
Programmed cell death responsible for tissue breakdown in interdigital regions
What mediates the apoptosis in the interdigital regions?
Bone morphogenic proteins
Describe the process of bone ossification in the limbs
Cartilaginous precursors develop by chondrofication within mesoderm in the 6th week
Primary centres of ossification appear in wks 8-12 in response to growth factors
(SO all endochondral ossification apart from clavicle)
Distinguish between endochondral and intramembranous ossification
Endochondral - cartilage precursor model laid down first (happens in long bones)
Intramembraneous - bone laid down directly into mesenchyme, occurs in flat bones
Define ossification
The process of laying new bone down by osteoblasts
During limb rotation, in which direction do the limb buds rotate?
Upper limb - 90 degrees laterally
Lower limb - 90 degrees medially
What happens, in relation to nerve development in the limb in the 5th week?
In the 5th week, peripheral nerves grow developing limb plexuses (brachial/lumbosacral) into the mesenchyme of the limbs
Define amelia
Total absence of limbs
Define meromelia
Partial absence of limbs
Define phocomelia
Some long bone absence, e.g. radius/fibula
Define micromelia
All parts present ut small
What is lobster claw foot?
Splitting of the footplate
Can be inherited as an autosomal dominant trait
What is the critical period for limb development?
24-36 days after fertilisation
Define polydactyly
Presence of more than 5 digits on the hands/feet
Extra digit incompletely formed and lacks muscular development
What may cause polydactyly?
Alcohol, thalidomide, inherited traits
Define syndactyly
Webbing of hands/feet
Common birth detect
More common in feet as opposed to hands
Define cutaneous syndactyly
Simple webbing between digits
Define osseous syndactyly
Fusion of bones, notches between digital rays fail to develop
What can thalidomide use in early pregnancy lead to?
Amelia/meromelia, intestinal atresia, cardiac abnormalities
What is the other name for congenital clubfoot?
Tapiles equinovarus
What is club foot?
Sole of foot turned medially and foot inverted
What causes club foot?
Multifactorial - genetic and environmental factors
?Abnormal positioning/restricted movement of foetus’s lower limb in utero
What may cause abnormal development of the hip?
Common after breech deliveries - ?breech posture during late pregnancy (abnormal development of acetabulum and head of femur)
General joint laxity may be attributed to many factors and is associated with congenital dislocation of the hip
When is the sensitive period of thalidomide use?
4-8 weeks
Why does thalidomide lead to the problems previously mentioned?
It disrupts cell adhesion and angiogenesis in the embryo
