embryology of the limbs Flashcards
limbs, arising from paraxial mesoderm i.e. somites
- Dermatome gives rise to connective tissue of the dermis
* Myotome gives rise to limb muscles
limbs, arise from lateral plate mesoderm
- Bones of upper and lower limb
- Blood vessels
- Connective tissue (except for that of the dermis)
(sensory nerve elements are derived from neural crest)
limb growth and patterning
- occurs during weeks 4-8
- firstly as cartilage
- limb buds appear at about 4 weeks, much of the basic structures of the limbs (bone and muscle groups) established by 8 weeks
- after 8 weeks. the limb elements then just increase in size
proximo-distal growth and patterning
- limb outgrowth initiated by the apical ectodermal ridge (AER) at the tip of the limb buds and proceeds from proximal (i.e. shoulder or hip) to distal (i.e. had or foot); i.e. proximal elements (humerus/femur) are formed prior to distal elements (ulna/tibia)
- process is dependent on FGF signalling and/or formation and maintenance of the AER will result in arrested limb development
HOX genes
- subset of homeobox genes
- group of related genes that specify regions of the body plan of an embryo
- Hox proteins encode and specify the characteristics of ‘position’
proximo-distal growth and patterning
- also dependent on HOX genes to specify each of the elements
- Disruption of HOX genes (via mutation or teratogens such as retinoic acid or ethanol) will therefore result in the loss of specific limb elements
dorso-ventral patterning
Specifies the dorsal surface (e.g. extensors) vs. ventral surface (flexors, palm/sole) of the limbs
Dorsal (Wnt7) and Ventral (BMPs and Engrailed-1) signalling factors are antagonistic.
This is what sets up the AER specifically at the tip of the limb bud, so disruption of D-V signals will not only affect D-V patterning, but can also affect proximo-distal growth as well.
anterior-posterior patterning
- anterior means towaerds the head
- the thumb and radius are ‘anterior’, little finger an dulna are ‘posterior’
- A-P patterning is established by the Zone of Polarizing activity (ZPA) on the ‘posterior’ side of the limb- the little finger side.
- Shh signalling from the ZPA specifically signals the formation of posterior elements
- Loss of the ZPA results in loss of posterior elements
- Upregulation of ZPA signals results in additional posterior elements (e.g. polydactyly on hypothenar side of hand)
- Duplication of the ZPA results in duplication of posterior elements (e.g. little fingers on both sides of the thumb)
regulation of growth and patterning
- signalling of ZPA also essential for maintaining AER
- limbs too long is ZPA signals upregulated, limbs to short if ZPA signalling is lost
- posterior elements e.g. little finger/ulna are formed prior to anterior elements e.g. radius/thumb
- > disruption of A-P patterning and growth can also result in loss of anterior elements
separation of digit rays
- the digits are initially interconnected by tissue which then regresses via apoptosis to produce separate digits
- apoptosis of interdigital tissue is dependent on BMP signalling within the interdigital tissue under the influence of Shh from the ZPA
- disruption of this process can therefore result in syndactyly, most often affects digits 3, 4 and 5
development of limb bones is via endochondral ossification
- mesenchyme begins to form chondrocytes
- chondrocytes lay down a ‘model’ of the bone
- blood vessels invade the model and osteoblasts localise and proliferate only at the epiphyses (ends)
- chondrocytes nearest the shaft (diaphysis) undergo hypertrophy, become calcified and undergo apoptosis
- growth of the long bones continues into early adulthood. this is maintained by FGF signalling to cause proliferation of chondrocytes in the growth plates
- long bones have 2 growth plates, in smaller bones (phalanges), there is only one at the tip
development of the body musculature
derived from paraxial mesoderm (somites)
- sclerotome, which develops into vertebral and rib bones
- myotome which develops into muscle
- dermatome, develops into dermal CT
myotome
- develops into muscle. further divided into:
1) primaxial myotome: adjacent to neural tube- affected by signalling factors from the neural tube to generate muscle precursors with limited migratory potential
2) abaxial myotome: ventrolateral myoblasts- respond to signals from the adjacent lateral plate mesoderm and ectoderm to give rise to a migratory population
3) primaxial myotome- epaxial muscles of the back (innervated by dorsal rami) - hypaxial muscles of the body wall (prevertebrals, intercostals, “strap muscles”, scalenes, geniohyoid, proximal limb girdle (rhomboids, levator scapulae, and latissimus dorsi)] (innervated by VENTRAL rami)
4) abaxial myotome: ventrolateral myoblasts - respond to signals from the adjacent lateral plate mesoderm and ectoderm to give rise to a migratory population - muscle precursors that stream out into the body wall and limbs
achondroplastic dwarfism
bond growth disorder- short in stature with normal sized torso and short limbs.
occurs when there are defects in chondrocyte proliferation. premature closure of epiphyseal growth plates
Spondyloepiphyseal dysplasia congenita (abbreviated to SED more often than SDC)
- rare disorder of bone growth that results in dwarfism
- affects the bones of the spine and the ends of bones
- also often problems with vision and hearing.
- signs and symptoms are similar to, but milder than, achondrogenesis type 2 and hypochondrogenesis.
- subtype of collagen disease affecting collagen types II and XI
