Development of the Limbs Flashcards
when does development of the limbs begin?
end of 4th week
how does development of the limb buds begin?
activation of the mesenchymal cells in the somatic lateral mesoderm
what regulates the proximo-distal patterning of the limb buds?
homeobox genes
when does the upper limb bud appear?
day 24
when does the lower limb bud appear?
day 26
what does HOX gene expression result from?
a combination of the expression of SHH, FGF’s and WNT-7a
what HOXgenes are expressed in the upper limb?
9-13
how do limb buds elongate?
proliferation of mesenchye
where do the upper and lower limb buds develop from?
upper - caudal cervical segments
lower - lumbar and sacral segments
the apex of each bud the ectoderm thickens to form what?
apical ectodermal ridge
what is the AER?
multilayered epithelial structure restricted to the end of a limb bud
what does the AER do?
induces proliferation of the limb mesenchyme
the mesenchyme adjacent to the AER consists of what?
undifferentiated, rapidly proliferating cells
the mesenchyme proximal to the AER differentiated into what?
blod vessels and cartilage bone models
where there a progress zone in the limb buds?
behind the AER and in front of the cell differentiation area
describe the development of the hand and foot plates
The distal ends of the limb buds flatten into paddle-like hand and foot plates. By the end of the 6th week, mesenchymal tissue in hand plates has condensed to form digital rays. During the 7th week digital rays are formed in the foot plates. Apoptosis (programmed cell death) is responsible for the tissue breakdown in the interdigital regions.
what mediates apoptosis in the interdigital regions?
bone morphogenetic proteins
describe 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 8-12 in response to growth factors. Endochondral ossification for all limb bones
what kind of ossification in the clavicle?
membranous
describe limb rotation
The upper limb rotates 90° laterally so that the extensors are on the lateral and posterior surfaces. The thumb is now lateral. On the other hand, the lower limb rotates 90° medially so that the extensors are on the anterior surface and the hallux is medial.
what are birth defects of the limbs often associated with?
other defects
hereditary
teratogen
total absence of the limbs
amelia
partial absence of the limbs
meromelia
absence of some of the long bones
phocomelia
all parts are present but as small (limbs)
micromelia
what is the critical period of limb development?
24-36 days
describe polydactyly
This is when there is more than 5 digits on either the hands or feet. The extra digit is incompletely formed and lacks muscular development. This can be inherited, or teratogen induced.
describe syndactyly
These are common defects of the hand or foot. Cutaneous syndactyly is simple webbing between the digits and is a common limb defect, more common in the foot. Osseous syndactyly, fusion of the bones, occurs when notches between the digital rays fail to develop.
describe congenital clubfoot
Clubfoot is also known as talipes equinovarus and is a relatively common birth defect. The sole of the foot is turned medially, and the foot is inverted. The causes can be multifactorial (genetic and environmental factors. It is hypothesised that abnormal positioning or restricted movement of the foetus’s lower limb in utero could cause clubfoot.
describe developmental dysplasia of the hip
Abnormal development of the acetabulum causes 15% of infants to have congenital dislocation of the hip. It is common after breech deliveries. Possible breech posture during late part of pregnancy resulting in abnormal development of acetabulum and head of femur. Also associated with congenital dislocation of the hip is generalised joint laxity. Causes of this are multifactorial.
describe the effects of thalidomide
Thalidomide was used from 1957-1962 as a sleeping tablet and anti-sickness medication. It caused the absence or deformity of long bones, intestinal atresia and cardiac anomalies. It acts by disrupting cell adhesion and angiogenesis. It is still used today to help cancer, leprosy and AIDS patients.
