Limb Anatomy and Development

Question 1

What is a limb?

Answer 1

Jointed bony appendage + forelimb + hind limb

Question 2

List tetrapods (4 limbs)

Answer 2

Mammals, birds, reptiles, amphibians

Question 3

Structure of tetrapod limbs

Answer 3

3 axes:
- proximal-distal (shoulder-fingers)
- anterior-posterior (thumb-little finger)
- dorsal-ventral (back of hand-palm)

Question 4

Which germ layer forms most of the tissues in the limb?

Answer 4

Mesoderm:
- bone
- tendom
- dermis
- blood vessels

Question 5

What is Hind limb

Answer 5

Lower limb of the body – sometimes known
as pelvic appendages

=> thigh and leg

Question 6

What is the Fore limb

Answer 6

Upper limb of the body – sometimes
known as pectoral limb

=> arm and forearm

Question 7

Stylopod

Answer 7

refers to upper part of limb (connect body-joint)
=> 1 bone

Question 8

Zeugopod

Answer 8

refers to the
middle section of the limb
=> 2 bones

Question 9

Autopod

Answer 9

refers to the last
section of the limb
=> lots of bones

Question 10

Where do limbs come from?

Answer 10

“lobe-finned fish”, no limbs put precursors

Paired fins come from FIN FOLDS
Limbs are derived from LOBE FINS

Question 11

How did our limbs evolve?

Answer 11

• 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

Question 12

Which animals has a lot of fish?

Answer 12

Acanthodians

Question 13

Fin fold theory

Answer 13

Pectoral and pelvic fins are remnants of one big long lateral fin fold (lacks fossil evidence)

Question 14

What is Tujiaaspis?

Answer 14

Jawless fish discovered in 2022 with the first known lateral fins

Question 15

Polydactyly

Answer 15

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)

Question 16

Reduced digits

Answer 16

Horses => just 1 finger (digit III, middle finger)

=> Cursorial (running) animales

=> Ostriches

=> Three-toed jerboa

Question 17

Ways to make a wing using the forelimb

Answer 17

=> 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

Question 18

Alvarezsauridae

Answer 18

• 1 finger
• very short forelimb
• perhaps used to open termine nests

Question 19

Majungasaurus

Answer 19

• huge shoulder blades
• strong adduction

Question 20

What are some interesting ways that tetrapods have modified their limbs?

Answer 20

• Wings
• Hooves
• Limb reduction

Question 21

Limb buds

Answer 21

Forelimb buds form on the 24th day
Hindlimb buds on 28th day

Question 22

What are the limb buds composed of?

Answer 22

EPIDERMAL JACKET ENCLOSING LATERAL PLATE MESODERM, from somatic layer

Question 23

What is located at the distal end of the limb bud?

Answer 23

A ridge, known as Apical Ectodermal Ridge (AER)

(Even though most of the tissued in the limb are mesoderm derivatives)

Question 24

Order of differenciation in the limbs

Answer 24

1) Humerus (femur)
2) Radius and ulna (tibia and fibula)
3) Carpals (tarsals)
4) Metacarpals (metatarsals)
5) Phalanges

Question 25

What is endochondral ossification

Answer 25

Cartilage being replaced by bone

Question 26

Endochondral ossification

Answer 26

Mesenchyme forms rudiment of limb bone

Chondrocytes synthesize cartilage

Question 27

Innervation of the Limb

Answer 27

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

Question 28

Human Limb Defects

Answer 28

0.1-0.2% live births

autosomal dominant genetic mutations:
- Grieg syndrome (GLI3 mutation)
- Apert syndrome (FGFR2)
- Holt-Oram syndrome (TBX5)

Question 29

AER

Answer 29

Requiered for Limb Outgrowth, may be source of mitogen

(John Saunders experiment)

Question 30

FGF

Answer 30

• stimulates formation of extra limb (may be wing or leg or both - a chimera)

Question 31

Proximal-Distal Patterning

Answer 31

2 signal model:
Proximal fates (eg. humerus) = specified by Retinoic Acid from SOMITE
Distal fates = specified by FGF from AER

Question 32

What does Shh induce?

Answer 32

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

Question 33

What does Shh regulates to govern A/P fates?

Answer 33

HoxD cluster expression

Question 34

Name a Shh mutation

Answer 34

Archeiropodia => extremely rare birth defect characterized by absence of distal limb structures

Caused by mutations that decrease SHH expression in the limb bud

Question 35

What does Shh promotes?

Answer 35

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)

Question 36

What are Tbx4 and Tbx5?

Answer 36

Transcription factors
Tbx5 in forelimbs
Tbx4 in hindlimbs

Question 37

In humans, mutations of TBX5 can cause…

Answer 37

Holt-Oram syndrome. Only affects the arms.

Question 38

Phocomelia can happen if

Answer 38

Thalidomide is given to pregnant women.
=> long bones are short and the hands/ feet malformed