Limb Development Flashcards
When do limb buds form
week 4
when do digits separate
week 8
when does primary ossification occur
week 12
What 3 things doppelgänger’s limbs develop from
1) somite (paraxial) mesoderm: muscles
2) Somatic (lateral plate) mesoderm: cartilage and bone
3) somatic (lateral plate) mesoderm: connective tissue
Collectively they are limb-forming mesoderm
Explain limb formation starting with what Limb-Forming mesoderm releases
1) Limb-forming meso term releases FGF-10, which induces the AER (apical ectodermal ridge) to release FGF-4 and FGF-8
2) FGF-4 and FGF-8 stimulate the limb-forming mesoderm to proliferate, causing growth in the proximal to distal direction
Where do limb buds appear?
Under the AER
When do individual bone structure begin to differentiate
during proliferation of the limb-forming mesoderm
What do the stylopod, zeugopod and autopod form
1) stylopod - humerus and femur
2) zeugopod - radius/ulna, fibia/tibia
3) autopod - carpals, metacarpals, digits, tarsal, metatarsals, digits
When do upper limb and lower limb buds appear?
upper limb - 24 days
lower limb - 1-2days later
What occurs during Week 4
Limb buds form
What occurs during Week 5
- Hand and foot plates form
- chondrofication (cartilage) centers appear
- Limbs are LATERALLY & CAUDALLY facing
What occurs during Week 6
Digital rays of hand form (somatic lat. plate mesoderm. condensing into digit shape)
Entire limb is CARTILAGINOUS
Libs BEND ANTERIORLY
What occurs during Week 7
Digital rays of feet form (somatic lat. plate mesoderm. condensing into toe-like shape)
Osteogenesis of long bones
Upper limbs – rotate laterally 90degrees
Lower limbs – rotate Medially 90degrees
What occurs during Week 8
Separate digits form due to APOPTOSIS of extra tissue which is stimulated by BMP
Lower limbs – “Barber pole” dermatome formation occurs
Limb musculature is derived from ___ and occurs during ___
dorsolateral cells of the somite
week 5
Explain how blood supply forms in the Upper limbs
Dorsal Aorta —> Intersegmental A. (enter limb bud) —> Primary Axial Artery —> Brachial A. ——(REMODLING OF ARTERIES TO CREATE ANATOMICAL VARIATION)—–> the limbs we’re born with
Explain how blood supply forms in the lower limbs
Aorta —-> Intersegmental A. (enter limb bud) —–> Primary Axial A. —–> Deep Artery of the Thigh —-(REMODLING)—–> Leg Arteries
Talipes Equinovarus
aka Club Foot
- Most common MSK defect
- 2x more in males
- sole of foot turned medially and is inverted
- ALL structure present, cases can be treated with casting
Developmental Hip Dysplasia
- more common in women
- underdevelopment of the acetabulum, dislocation of femur from hip joint
- Clinical = joint laxity
Proximo-distal Limb Patterning
Mesenchyme releases FGF-10, AER is stimulated to release FGF-4 and FGF-8 (continues in a cycle)
What do Hox genes do?
Regulate types, shapes and positioning of bones
Tuning them off/on at specific times is what dictates shape/type/position
Dorso-ventral patterning
Ventral Surface (Flexor muscles) = BMPS Dorsal surface (Extensor muscles) = Wnt7
Anterior-Posterior Patterning
- Established by the Zone of Polarizing Activity (an area of mesenchyme that directs ant/post axis)
- ZPA releases SHH and Retinoic Acid which signals the posterior elements
Posterior first —-> Anterior follows after
Clinically, why is it important that posterior elements from before anterior elements
Defects in posterior elements (little finger/ulna) formation and disruption of A-P patterning and growth can result in problems/loss of anterior elements (thumb/radius)
What happens if there is a:
1) Loss of ZPA
2) Upregulation of ZPA
3) Duplication of ZPA
1) loss of posterior elements (digit or ulna)
2) Additional posterior elements (Polydactyly - extra digit)
3) duplication of posterior elements (little fingers on both sides of thumb
Explain the following clinical limb development issues:
1) Polydactyly
2) Syndactyly
3) Bradydactyly
4) Meromelia
5) Phocomelia
6) Amelia
7) Arthrogryposis
8) Ectodactyly
1) extra digit, upreg of ZPA (Week 6 and 7 for hands and feet respectively)
2) Fusion of digits – failure of BMP to apoptosis the tissue
3) Short digits —- failure of BMP to to apoptosis tissue
4) Part of limb is absent (during week 4)
5) Type of Meromelia where the hands and feet are close to the body -issues with FGF signaling during WEEK 4
6) No limb bud formed — THALIDOMIDE
7) Congenital joint contractures – neurological defects, joint/contiguous tissue problems
8) Split Foot/Hand (looks like a claw) —- Center of aER did not develop properly (WEEK 6 for hand……WEEK 7 for foot
