Development of Limbs Flashcards
When does the development of limbs begin?
Near the end of the 4th week
What is activated in the somatic lateral mesoderm?
Mesenchymal cells
What regulates patterning?
Homeoxbox genes
When do the upper limb buds apper?
Day 24
When do the lower limb buds appear
1 to 2 days after the upper limb ones
Explain HOX genes
Regionally expressed in limbs and determine which skeletal element formed
HOX gene expression results from a combination of the expression of SHH, FGF’s and WNT-7a
What HOX genes form the upper limb?
HOXd 9-13
What happens if HOXa 11 and HOXd 11 are removed?
Radius and ulna do not form
What are limb buds elongated by?
Proliferation of mesenchyme
What do upper limbs buds develop opposite?
The caudal cervical segments
What do the lower limb buds form opposite?
The lumbar and sacral segments
What happens at the apex of each limb bud?
Ectoderm thickens to form and apical ectodermal ridge
What is AER restricted to?
End of limb bud
What is the apical ectodermal ridge?
Multilayered epitherlial structre
Exerts an inductive influence on the limb mesenchyme
What does the mesenchyme ajacent to the AER consist of?
Undifferentiated rapidly proliferating cells
What do mesenchymal cells proximal to the apical ectodermal ridge differentiate into?
Blood vessels and cartilage bone models
What do the distal ends of the limb buds flatten into?
Paddle-like hand plates and flipper- like foot plates
What has happened by the end of the 6th week to mesenchymal tissue in hand plates?
Condensed to form digital rays
What happens during the 7th week to foot plates?
Digital rays are formed in the foot plates
What does the development of the hands look like?
What does the development of the feet like?
What is programmed cell death responsible for?
The tissue breakdown in the interdigital regions –mediated by bone morphogenetic proteins
What do cartilagionous precursors of the limb bones develop by?
Chondrification within the mesoderm in the 6th week
When do primary centres of ossification appear?
Weeks 8 to 12 in response to growth factors
What occurs in all bones in limbs development except the clavicle?
Enodochrial ossification. Clavicle is membranous
What is limb rotation like?
Upper limbs and lower limbs rotate
Upper limbs rotate 90o laterally so that extensors are on the lateral and posterior surfaces (and the thumb is lateral)
Lower limbs rotate 90o medially so that the extensors are on the anterior surface (and the big toe is medial)
Upper limb dermatomal development. Draw it!
Lower limb dermatomal development. Draw it!
What grows into the mesenchyme of the limbs?
During the 5th week, peripheral nerves grow from the developing limb plexus
(brachial and lumbosacral) into the mesenchyme of the limbs
What is total absence of limbs called?
Amelia
What is partial absence of limbs called?
Meromelia
What is some long bones absence called?
Phocomelia
What is it called with all long bones present but small?
Micromelia
What is the inheritance pattern of lobster claw foot?
Autosomal dominant triat
What is the critical period of limb development?
24-36 days after fertilization
What is polydactyly?
Presence of more than 5 digits on hand or feet
Extra digit is incompletely formed and lacks muscular
development
May be inherited or teratogen induced
What is syndactyly?
Common birth defect of the hand and foot
Cutaneous Syndactyly (simple webbing between the digits) is a common limb defect
More frequent in the foot than in the hand
Osseous Syndactyly (fusion of bones) occurs when notches between the digital rays fail to develop
What was thalidomide used as?
1957-1962 used as a sleeping tablet and anti-nauseant
What does thalidomide cause?
Absence or deformity of long bones (intestinal atresia and cardiac anomalies)
‘Sensitive’ period 4-8wks
Acts by disrupting cell adhesion and angiogenesis
What is thalidomide used for?
Used to help cancer, leprosy and AIDS patients
What is congenital clubfoot called?
Talipes Equinovarus
What does talipes equinovarus look like?
Sole of the foot is turned medially and the foot is inverted
What is the cause of congenital clubfoot?
Multifactorial (genetic and environmental factors)
Abnormal positioning or restricted movement of the fetus’s lower limb in the utero – Evidence is inconclusive
What percentage of patients with congenital disloavtion of the hip have abnormal develop of acetabulum?
15%
When is abnormal develop of the acetabulum common?
Common after breech(buttocks) deliveries -? Breech posture during late part of pregnency (abnormal development of acetabulum and head of femur)
What is generalised joint laxity?
Multifactoril
Associated with congenital disloaction of hip
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