Limbs Flashcards
What weeks does human limb development take place?
4-8
Which limb begins to develop first, how much before?
Upper limb couple days before lower limb
What drives proximal distal limb patterning?
Limb grows progressively, digits forming last
Progress zone model: cells spend shorter time in the zone form more proximal structures than those staying longer
What drives anterior posterior/craniocaudal (i.e. thumb to little finger) patterning of limb?
Patterned by signals from ZPA (mesenchymal cells at posterior limb margin - zone of polarising activity).
Cells closest to it form posterior structures.
What forms dorsal/ventral patterning of limb (i.e. back or palm of hand)?
Pattern controlled by non ridge ectoderm,
How does the limb formation begin?
Mesenchymal cells from the lateral plate mesoderm proliferate to the point that they cause the ectoderm above to bulge out, forming a limb bud
What mesoderm contributes to the limbs?
Lateral plate mesoderm
What creates the progress zone that drives proximal distal limb patterning?
The apical ectodermal ridge (AER) creates and maintains a zone of cell proliferation known as the progress zone
What is the AER?
An organizer at the end of the limb bud, called the apical ectodermal ridge (AER). Drives cell proliferation.
What patterns the digits?
Gradient of Shh, highest in 5th digit, lowest in 1st
What creates the Shh gradient for generating craniocaudal patterning?
ZPA
What digit forms on the side of the ZPA?
5th
When do hyaline cartilage models of the bone form?
Start in 6th week, full set by end of 6th week
By what week are there primary ossification centres in all bones?
12
Is limb identity specified before they grow out (i.e. upper limb vs lower limb)?
Yes
What does early limb bud consist of?
Lateral plate mesoderm - skeletal elements covered by ectoderm (cuboidal epithelium)
What drives limb bud outgrowth?
Reciprocal epithelial mesenchymal interactions between these cells governs limb initiation and outgrowth.
What happens to overlying ectoderm as limb buds out?
Thickens and forms apical ectodermal ridge AER (which edges distal tip of bud)
What signalling allows bud outgrowth?
Signalling between AER and progress zone
AER induces growth of underlying mesenchyme so mesodermal growth causes limb bud to grow
Also mesenchyme signals back to AER
How does bone grow in limb?
Endochondral ossification
What are mesenchymal stem cells precursor for?
Chondrocytes
What are skeletal elements of limbs derived from?
Lateral plate mesoderm
What are skin and associated structures derived from?
Ectoderm
What are blood vessels derived from in limbs?
Angioblasts in mesoderm
Describe endochondral ossification
Chondrocytes form cartilage model
Chondroblasts in diaphysis undergo hypertrophy and apoptosis as they mineralise surrounding matrix, chondrocytes die - create cavities
Blood vessels invade - brings osteoblasts/osteoclasts
Osteoblasts and osteoclasts modify the calcified cartilage matrix into spongy bone - at birth diaphysis ossified
Dense, irregular connective tissue forms a sheath (periosteum) around the bones.
Epiphysial plate contains proliferating chondrocytes and continues to grow
What part of the bone continues to grow after birth?
Epiphysial plate (hyaline cartilage persists here)
What do muscles arise from?
Somatic mesoderm (myotome) which invades into limb
Dorsal/ventral muscle masses - dorsal extensor, ventral flexor muscles
How do nerves come together in limb development?
Ventral branches of spinal nerve (C5-T1) and (L4-S3) innervate limb muscles
Come together and form plexus at limb bud base before separated into dorsal and ventral branches and entering limb
What branches of spinal nerves innervate limb muscles?
(C5-T1) and (L2-S3)
Where do sensory neurones follow into limbs?
Follow motor neurones
Do motor nerves follow sensory nerves?
No, sensory nerves follow motor nerves
What sculpts axilla and separation of digits?
Apoptosis
Describe rotation of the limbs in development and what’s the effect?
Medial rotation of lower limb
Less pronouned lateral rotation of upper limb around long axis
Spiralling dermatomes
What happens to dermatomes as limb extends?
Ectoderm from body wall recruited as limb extends -pulls in dermatome regions from other dermatomes
What happens in achondroplasia?
Mutation in FGFR3 receptor gene
Constitutively active and cartilage doesn’t develop into bone and individual is shorter
What happens in gigantism?
GF and IGF1 are potentially in excess
Increased levels of growth hormone before the fusion of the growth plate which usually occurs at some point soon after puberty.
