Limb Development

Question 1

What week does limb development start? Does upper extremity or lower extremity develop first?

Answer 1

During week 4, upper extremity starts forming first

Question 2

What week do the digits start to form?

Answer 2

week 8

Question 3

What three things are involved in developing the limbs (cell wise)? (3)

Answer 3

Muscle from somite mesoderm (paraxial) (hypomere)

Cartilage from lateral plate somatic mesoderm

Connective tissue from lateral plate somatic mesoderm (mesenchymal)

Question 4

What consists of limb forming mesoderm?

Answer 4

Paraxial and lateral plate mesoderm

Question 5

What does FGF10 do and where does it come from?

Answer 5

From the limb-forming mesoderm, will stimulate surface ectoderm to become the apical ectodermal ridge (thickening of surface ectoderm needed for limb development)

Question 6

What will the apical ectodermal ridge release to stimulate limb mesoderm?

Answer 6

FGF 8 and 4

Question 7

Once the reciprical signaling occurs between the limb forming mesoderm and the apical ectoderm ridge (FGF 10,4 & 8), what occurs?

Answer 7

The limb cells will proliferate and will grow from proximal to distal

Question 8

What is unique of the limb-bud mesoderm?

Answer 8

the different areas of mesoderm are preprogrammed to become different regions of bone

Question 9

What are the three regions of the limb bud before growth and what do they form? (proximal, middle, distal (grow in that order) )

Answer 9

Stylopod, proximal: humerus and femur
Zeugopod, middle: radius/ulna, tibia/fubla
Autopod, distal region: carpals, metacarpals and digits, as well as tarsal, metatarsal and digits in foot

Question 10

What forms during week 5?

Answer 10

hand and foot plates, hand before foot (little paddles)

chondrification centers appear

Question 11

What forms/happens during week 6?

Answer 11

formation of digital rays of hands (somatic layer of lateral plate) bones/ beginning of digits

entire limb skeleton is cartilaginous

Question 12

What forms/ happens during week 7?

Answer 12

somatic mesoderm layer of lateral plate will condense to form bones/ digital rays of feet (beginning of digits)

osteogenesis of long bones begin, rotation of limbs

Question 13

What forms during week 8?

Answer 13

separate digits are formed due to apoptosis by BMP family (need BMP for cells to undergo apoptosis to separate fingers so we do not get webbed/fused fingers)

Question 14

Where do the upper limb bud and lower limb bud form in mytomes?

Answer 14

Upper arm: cervical region

Lower leg: lumbar/sacral region

Question 15

What is the difference in rotation of lower and upper limb by the end of week 7?

Answer 15

The upper limb rotates laterally 90 degrees

the lower limb rotates medially 90 degrees

hence why there is a huge difference

Question 16

For blood supply of the limbs, intersegmental arteries come from the dorsal aorta. What do the intersegmental arteries become in the upper and lower limb?

Answer 16

The primary axial artery

Question 17

What does the primary axial artery give rise to in the upper limb?

Answer 17

Common interosseous and brachial artery

Question 18

What does the primary axial artery give rise to in the lower limb?

Answer 18

deep artery of the thigh and the posterior tibial artery

Question 19

What occurs in club foot (every 1 in 1000 births)?

Answer 19

The foot is turned in medially and inverted, otherwise normal

Question 20

How is club foot generally fixed?

Answer 20

Casting, taping and in serious cases surgery

Question 21

What is developmental hip dysplasia (in more females)?

Answer 21

the under development of the acetabulum (hip socket) of the hip bone/ head of femur. a lead heart shaped cover is placed over the ovaries to do xray

Question 22

What is needed for proximo-distal growth and patterning?

Answer 22

the apical ectodermal ridge (from ectoderm) and the signaling of FGF 10 from limb-forming mesoderm and FGF 4 and 8 from the apical ectodermal ridge & HOX genes

Question 23

What is needed for dorso (extensors) -ventral (flexors) patterning?

Answer 23

The ventral surface is maintained by the BMPS and the dorsal surface is maintained by the Wnt7, this is set up by the apical ectodermal ridge (AER)

Question 24

What is needed for anterior posterior patterning of the limb?

Answer 24

Zone of polarizing activity (ZPA) on the posterior side of the limb (what would be the pinky finger area)

Question 25

What does the zone of polarizing activity (ZPA) release?

Answer 25

SHH and retinoic acid signals the posterior elements of digits 3-5

Question 26

What occurs when there is a loss, upregulation, or duplication of ZPA?

Answer 26

Loss: lose post. aspect/ digit

Upreg: additional digits/posterior aspects

Duplication: mirror image of little fingers on either side of thumb

Question 27

What is formed first, anterior or posterior elements

Answer 27

Posterior elements (ulna and little finger) are formed first, anterior elements (radius and thumb) are formed after

Question 28

A child has polydactyly (extra finger), what week did this abnormality occur and how?

Answer 28

Week 6 when the digital rays form, and it is caused by an upregulation of ZPA

Question 29

A child has polydactyly (extra three alongside thumb), what week did this abnormality occur and how?

Answer 29

Week 7 when foot digital rays form, caused by a duplicate ZPA zone, due to 3 extra/mirror digits

Question 30

A child has brachydactyly (short fingers), what week did this abnormality occur and how?

Answer 30

Due to proximal-distal growth abnormalities at apical ectodermal ridge, lack of FGF 10,4,8 (AUTOPOD)

week 6-8

Question 31

A child has syndactyl (fusion of toe), what week did this abnormality occur and how?

Answer 31

Week 8, down regulation of BMPs during week 8 needed for apoptosis to get separation of digits

Question 32

A childer has meromelia-phocomelia (short limbs commonly caused by thalidomide in 50s), what week did this abnormaily occur and how?

Answer 32

Weeks 3-4-5, apical ectodermal ridge issues, FGF 4&8 or lack of vasculature

Question 33

Amelia is where no upper limbs form, when does this occur?

Answer 33

Weeks 3/4

Question 34

Split hand/foot, also know as lobster claw or ectrodactyly (get first and 5th digit only), what week does it occur for hands and feet, and how?

Answer 34

**** IMPORTANT Center of apical ectodermal ridge was downregulated, and the middle fingers were not formed at all. Hands during week 6, feet during week 7

Question 35

What is arthrogryposis and what are the possible causes?

Answer 35

Congenital joint contractures

Due to: neurological defects, muscular abnormalities, joint and connective tissue problems and fetal crowding(no movement)