Embryology of limb development Flashcards
Limbs arise from which germ layers
Paraxial mesoderm (more specifically the somites) and lateral plate mesoderm
Somites give rise to the dermatomes (CT of the dermis ) and myotomes (limb muscles)
Lateral plate mesoderms becomes the bones of upper/lower limb, blood vessels, CT (except for dermis)
When does limb development occur
Weeks 4-8
Proximal-distal growth and patterning
Limb outgrowth in this direction is initiated by the apical ectodermal ridge (AER) and the tip of the limb buds
Proximal elements such as the shoulder/hip develop before the distal element e.g hand/foot
Dependent on fibroblast growth factor (FGF) being released by the AER; sends messages to mesenchyme to create cartilaginous templates
Role of HOX genes
Subset of homeobox genes
Group of related genes that specify the positions of different parts of the limbs
Dorsal-ventral patterning
Dorsal signalling (Wnt gene) Ventral signalling (BMPs and Engrailed-1)
Anterior-posterior patterning
Established by zone of polarising activity (ZPA) on the posterior side of limb (little finger side)
Sonic hedgehog signalling from ZPA signals posterior elements specifically
Posterior elements are formed prior to anterior elements
Regulation of growth and patterning
Upregulation of ZPA signals result in limbs that are too long
Loss of ZPA signals results in limbs that are too short
Separation of digit rays
Initially fingers are interconnected and then separated by apoptosis
Apoptosis is dependent on BMP (bone morphogenic protein) signalling under the influence of sonic hedgehog from the ZPA
Syndactyly occurs when digits don’t separate
Development of limb bones occurs via ___ ____
Endochondral ossification
Describe endochondral ossification
Blood vessels invade the cartilaginous template and osteoblasts proliferate at the epiphyses only (the ends)
Chondrocytes nearest the shaft undergo hypertrophy, become calcified and undergo apoptosis
Growth of long bones continues into early adulthood (maintained by FGF signalling)
Longer bones have two growth plates, small bones have one
Describe endochondral ossification
Blood vessels invade the cartilaginous template and osteoblasts proliferate at the epiphyses only (the ends)
Chondrocytes nearest the shaft undergo hypertrophy, become calcified and undergo apoptosis
Growth of long bones continues into early adulthood (maintained by FGF signalling)
Longer bones have two growth plates, small bones have one
Development of limb muscles
Myotome of paraxial mesoderm somites form the muscle
Myotome is split into:
primatial Myotome - adjacent to neural tube ; affected by signalling factors from neural tube to give rise to muscle with limited migratory potential ; muscles of spine/body wall
abaxial Myotome - ventrolateral my oblasts which respond to signals from the adjacent lateral plate mesoderm and ectoderm to give rise to a migratory population (limb muscles)
C5-T1 myotomes are in line with the limb bud
Achrondroplastic dwarfism
Short in stature with a normal sized torso but short limbs
Occurs when there are defects in chondrocyte proliferation = premature closure of epiphyseal growth plates
Spondyloepipheseal dysplasia congenita (SED)
Rare disorder that results in dwarfism
Spine and ends of bones are shortened ; problems with vision and hearing
Subtype of collagen disease affecting type II and XI
Amelia and phocomelia
Limb absence - Amelia ; early loss of FGF
Shortened limbs - phocomelia ; partial loss of FGF or HOX mutation
Primatial Myotome becomes which muscles and how are they innervated
Epaxial muscle of the back (innervated by dorsal rami)
Hypaxial msucles of the body wall
Prevertebrals, intercostals, strap muscle, scalenes, geniohyoid, rhomboid, levator scapulae, latissimus Dorsi (innervated by ventral rami)
