Limb Anatomy and Development Flashcards
What is a limb?
Jointed bony appendage + forelimb + hind limb
List tetrapods (4 limbs)
Mammals, birds, reptiles, amphibians
Structure of tetrapod limbs
3 axes:
- proximal-distal (shoulder-fingers)
- anterior-posterior (thumb-little finger)
- dorsal-ventral (back of hand-palm)
Which germ layer forms most of the tissues in the limb?
Mesoderm:
- bone
- tendom
- dermis
- blood vessels
What is Hind limb
Lower limb of the body – sometimes known
as pelvic appendages
=> thigh and leg
What is the Fore limb
Upper limb of the body – sometimes
known as pectoral limb
=> arm and forearm
Stylopod
refers to upper part of limb (connect body-joint)
=> 1 bone
Zeugopod
refers to the
middle section of the limb
=> 2 bones
Autopod
refers to the last
section of the limb
=> lots of bones
Where do limbs come from?
“lobe-finned fish”, no limbs put precursors
Paired fins come from FIN FOLDS
Limbs are derived from LOBE FINS
How did our limbs evolve?
- Tetrapod digits and ray-finned fish rays share the same genetic regulation
- Tetrapod zeugopod and stylopod = derived from the ancestral fin region called the metapterygium
Which animals has a lot of fish?
Acanthodians
Fin fold theory
Pectoral and pelvic fins are remnants of one big long lateral fin fold (lacks fossil evidence)
What is Tujiaaspis?
Jawless fish discovered in 2022 with the first known lateral fins
Polydactyly
In cats => can occur as a result of mutation that causes ectopic expression of Shh in the developping limb bud (6 toes)
Key west and Kingston-upon-Hull
Pandas & moles => “false thumb”, elaborated wrist bone
Humans => pretty rare (2 in 10.000)
Reduced digits
Horses => just 1 finger (digit III, middle finger)
=> Cursorial (running) animales
=> Ostriches
=> Three-toed jerboa
Ways to make a wing using the forelimb
=> BIRDS: 3 digits, wing surface made of feathers, fused carpals and metacarpals
=> PTEROSAURS: wing made of skin, supported by elongated pinky finger
=> BATS: wing made of skin, supported by elongated fingers 2,3,4,5
=> YI QI
Alvarezsauridae
- 1 finger
- very short forelimb
- perhaps used to open termine nests
Majungasaurus
- huge shoulder blades
- strong adduction
What are some interesting ways that tetrapods have modified their limbs?
- Wings
- Hooves
- Limb reduction
Limb buds
Forelimb buds form on the 24th day
Hindlimb buds on 28th day
What are the limb buds composed of?
EPIDERMAL JACKET ENCLOSING LATERAL PLATE MESODERM, from somatic layer
What is located at the distal end of the limb bud?
A ridge, known as Apical Ectodermal Ridge (AER)
(Even though most of the tissued in the limb are mesoderm derivatives)
Order of differenciation in the limbs
1) Humerus (femur)
2) Radius and ulna (tibia and fibula)
3) Carpals (tarsals)
4) Metacarpals (metatarsals)
5) Phalanges
What is endochondral ossification
Cartilage being replaced by bone
Endochondral ossification
Mesenchyme forms rudiment of limb bone
Chondrocytes synthesize cartilage
Innervation of the Limb
Spinal neves C5-T2 => forelimb
L4-S3 => hindlimb
Both invade limb bud
Limb muscles = not resposible for attracting axons to limb bud but they regulate final branching pattern in the limb
Human Limb Defects
0.1-0.2% live births
autosomal dominant genetic mutations:
- Grieg syndrome (GLI3 mutation)
- Apert syndrome (FGFR2)
- Holt-Oram syndrome (TBX5)
AER
Requiered for Limb Outgrowth, may be source of mitogen
(John Saunders experiment)
FGF
- stimulates formation of extra limb (may be wing or leg or both - a chimera)
Proximal-Distal Patterning
2 signal model:
Proximal fates (eg. humerus) = specified by Retinoic Acid from SOMITE
Distal fates = specified by FGF from AER
What does Shh induce?
Digit Duplication
ZPA (Zone of Polarizing Activity) -organizing centre- expresses Shh and when this protein is expressed in the anterior limb bud => causes a mirror-image duplication of the digits identical to that of ZPA graft
Shh from ZPA acts as a morphogen specifying different digits at different concentrations
Highest = most posterior
Lowest = most anterior
What does Shh regulates to govern A/P fates?
HoxD cluster expression
Name a Shh mutation
Archeiropodia => extremely rare birth defect characterized by absence of distal limb structures
Caused by mutations that decrease SHH expression in the limb bud
What does Shh promotes?
Limb Outgrowth (overgrowth)
No Shh in limb bud => distally truncated limbds with few digits
No Gli3 => increase in Shh activity => polydactyly (like human Grieg Syndrome)
What are Tbx4 and Tbx5?
Transcription factors
Tbx5 in forelimbs
Tbx4 in hindlimbs
In humans, mutations of TBX5 can cause…
Holt-Oram syndrome. Only affects the arms.
Phocomelia can happen if
Thalidomide is given to pregnant women.
=> long bones are short and the hands/ feet malformed
