Limb Development

Question 1

Skeletal muscle is from:

Answer 1

Hypomere. Somite mesoderm.

Question 2

Cartilage and CT is from:

Answer 2

Somatic laterl plate mesoderm.

Question 3

Primary ossification occurs in:

Answer 3

Wk 12

Question 4

Stylopod
Zeugopod
Autopod

Answer 4

Stylopod: humerus and femur (proximal).
Zeugopod: radius/ulna and tibia/fibula (middle).
Autopod: carpals, metacarpals, digits, tarsals, metatarsals, digits.

Question 5

Week 5

Answer 5

Hand and foot plates develop.

Chondrificaion centers appear.

Question 6

Week 6

Answer 6

Distal rays of hand form.

Entire skeleton is cartilaginous.

Question 7

Week 7

Answer 7

Distal rays of feet form.
Osteogenesis begins.
Limbs rotate.

Question 8

Week 8

Answer 8

Separate digits form.

Apoptosis via BMP.

Question 9

Limb development overview

Answer 9

Limb forming mesoderm releases FGF 10 which stimulates surface ectoderm. Surface ectoderm thickens to create AER. AER releases FGF 8/4 which stimulates limb mesoderm and begins proximodistal growth.

Question 10

Limb rotation weeks 5-7

Answer 10

Wk 5: U/L limbs go lateral and caudal.
Wk 6: Limbs bend anteriorly..
Wk 7: UL externally rotate and LL internally rotate 90 degrees.

Question 11

Blood supply to UL

Answer 11

Aorta branches to intersegmental As. Intersegmental As enter limb bud and beocme a primary axial A. Primary axial A gives rise to Brachial A and Common interosseous A. Remodeling occurs.

Question 12

Blood supply to LL

Answer 12

Aorta to primary axial to deep A of thigh to Posterior tibial A of thigh. Then remodeling.

Question 13

Club foot

Answer 13

Most common MSK defect.
Foot internally rotated and inverted.
2x more common in males.
All structures present and likely can be fixed.

Question 14

Developmental hip dysplasia

Answer 14

More common in females.
Under development of acetabulum.
Joint laxity.

Question 15

Proximodistal growth

Answer 15

AER proceeds based on FGF signaling. HOX genes determine shape and length of bones.

Question 16

Dorsoventral growth

Answer 16

Ventral surface maintained by BMPs
Dorsal surface maintained by Wnt7.
AER sets up these axices and tells cells to secrete these molecules.

Question 17

Anterior-posterior growth

Answer 17

Established by ZPA on posterior pinky side. ZPA will signal with SHH and retinoic acid and develop digits 5-3 and the ulna.

Question 18

Loss of ZPA results in:

Answer 18

Loss of posterior elements (i.e. loss of ulna, one of digits 5-3).

Question 19

Upregulation of ZPA signals results in:

Answer 19

Additional posterior elements (i.e. polydactyly).

Question 20

Duplication of ZPA resulst in:

Answer 20

Duplication of posterior elements (i.e. little fingers on both sides of thumb).

Question 21

Due to posterior elements being formed first…

Answer 21

Disruption of the A-P patterning can also cause loss of anterior elements (radius, thumb).

Question 22

Polydactyly of hand

Answer 22

Wk 6

Upregulation of ZPA

Question 23

Brachydactyly

Answer 23

Wks 6-8
Issues with FGF 10, 8,or 4.
Short fingers.

Question 24

Syndactyly

Answer 24

Wk 8

Down regulation of BMPs.

Question 25

Meromelia

Answer 25

Wks 3-5
Intermediate to late loss of FGF signaling.
Missing part of limbs)

Question 26

Amelia

Answer 26

Wks 3-4.
Early loss of FGF signaling.
No arms.

Question 27

Split hand/foot (Lobster claw or Ectrodactyly)

Answer 27

Split hand (wk 6) and split foot (wk 7)
Center of AER downregulated and no digits are formed.
Partial loss of FGF 8.

Question 28

Arthrogryposis

Answer 28

Joint contracture (shortening).
Unclear cause, but thought to be due to neurological effects, muscular abnormalities, joint/cartilage issues, or fetal crowding.

Question 29

Phocomelia

Answer 29

Loss of long bones.
Partial loss of FGf signaling of HOX disruption.
From thalomide,