Limb Development

Question 1

Why are limbs important?

Answer 1

To break it down in da club after QUARANTINE!

Question 2

When do upper and lower limb buds form?

Answer 2

4th week
Upper - 24 days
Lower- 25-26 days

Question 3

What is the apical ectodermal ridge (AER)?

What happens there?

Answer 3

A thick band of ectoderm where limb buds form.

Mesenchyme proliferate and grow from ateral plate mesoderm (limb buds now bulge)

Question 4

Regions of limb outgrowth

Answer 4

Stylopod- humerus or femur
Zeugopod- radius and ulna; tibia and fibula
Autopod- hands/ feet

Question 5

Axes of limb bud?

Answer 5

Proximal-Distal (Shoulder-Digits) FGF signalling & HOX
Cranial-Caudal (Hallu- Phalanx V) SHH & HOX
Dorsal-Ventral (Dorsum-Palm) Wnt7a and Engrailed (En1)

Question 6

What growth factor induces AER?

Answer 6

FGF10

Question 7

What does AER secrete?

Answer 7

FGF8 (bc positive feedback from FGF10)

Question 8

FGF and AER make what axis?

Answer 8

Proximodistal

Question 9

Manipulating AER (early, late, and transplant)

Answer 9

Early removal: only 1st segment
Late removal: 1st and 2nd segments
Transplanting: supernumerary digits

Question 10

Meromelia

Answer 10

‘partial-limb’

intermediate to late loss of FGF

Question 11

Amelia

Answer 11

‘no-limb’

early loss of FGF signaling

Question 12

Phocomelia

Answer 12

‘seal’s-limb’ loss of long bones
Partial loss of FGF signalling
OR thalomide disrupting HOX

**thalomide used to be taken during pregnancy

Question 13

Adactyly

Answer 13

Absent digits

Late loss of FGF

Question 14

Ectrodactyly

Answer 14

Split hand. ‘Lobster claw’
Partial absense of FGF8 from AER
1.5:100,000
(EEC)- ectrodactly- ectodermal dysplasia, cleft palate

Question 15

Zone of Polarizing Activity (ZPA) makes ___ axis?

By expressing what?

Answer 15

craniocaudal

SHH

Question 16

What digit is most likely to form in absence of SHH?

Answer 16

Digit 1 (cranial end)

Question 17

How does Polydactyly occur?

Answer 17

Overexpression of SHH causes 2nd ZPA to form (now in cranial and caudal end)
Extra digits lack normal musculature

Question 18

HOX genes regulate what axes?

Answer 18

craniocaudal & proximodistal

Question 19

HOX9-10 paralogs

Answer 19

specifies stylopod (HOX9=scapula)

Question 20

HOX11 paralogs

Answer 20

specifies zeugopod

HOX 9-11

Question 21

HOX12-13 paralogs

Answer 21

specifies autopod

HOX9-13

Question 22

Brachydactyly and its genetics?

Answer 22

shortening of fingers and toes 
Genetic change in HOXD13 (finger gene)
OR PTHLH (parathyroid hormone like hormone)
Autosomal dominant

Question 23

What regulates dorsal ventral Axis?

Answer 23

Wnt7a: expressed in dorsal ectoderm
Engrailed (En1): expressed in ventral ectoderm.
- Prevents Wnt7a. restricts positioning of AER to establish dorsoventral

Question 24

What signals digit formation?

Answer 24

High BMP = High cell death of cutaneous webbing

Question 25

When do digital rays form in hand plates?

Answer 25

by 6th week day 41 limb is cartilagenous

Question 26

When do digital rays form in foot plates?

Answer 26

by 7th week day 46 osteogenesis begins

Question 27

When do separate digits form?

Answer 27

by 8th week upper: day 52 lowwer: day 56

Question 28

What is syndactyly?

Answer 28

fused digits because digital rays failed to develop

Question 29

What is cutaneous syndactyly?

Answer 29

webbing present because low BMP

Question 30

What is osseous syndactyly?

Answer 30

Synostosis (bone fusion) Failure to form interdigit notch HOXD13 (finger gene) Auto dominent

Question 31

What does the dorsal limb muscle mass form?

Answer 31

Upper: extensor and suppinators Lower: extensor and abductors

Question 32

What does the ventral limb muscle mass form?

Answer 32

Upper: Flexors and pronators Lower: Flexors and adductors

Question 33

Where do limb tendons arise from?

Answer 33

Lateral plate mesoderm | vertebral tendons from paraxial

Question 34

When does limb innervation begin?

Answer 34

5th week | Motor neurons innervate 1st, then sensory

Question 35

What innervates the limb's dorsal muscle mass?

Answer 35

dorsal branches of ventral rami (these are not epaxial)

Question 36

What innervates the limb's ventral muscle mass?

Answer 36

ventral branches of ventral rami

Question 37

Dorsal aorta gives rise to ______ which give rise to ______

Answer 37

intersegmental arteries | primary axial arteries and its branches

Question 38

Describe vascular development path of upper limb

Answer 38

Primary Axial a. --> brachial a. & common interosseous a. --> ulnar & radial a.

Question 39

Describe vascular development path of lower limb

Answer 39

Primary Axial a. --> deep artery of thigh --> anterior & posterior tibial a.

Question 40

When do limb buds rotate? What limbs are doing what? | Osteogenesis also begins at this time

Answer 40

Week 7 Upper: 90 laterally Lower: 90 medially

Question 41

What can amniotic bands do?

Answer 41

When there is too little amniotic fluid, amniotic bands stick to fetal structure and cut off growth.

Question 42

What is bilateral talipes equinovarus

Answer 42

'Club foot' oligohydramnios reduces fetal movement too litlle amniotic fluid compresses fetus hindering outward rotation of limbs 1:1000

Question 43

When does primary ossification begin?

Answer 43

Week 12. | this isn't osteogenesis