Limb Development

Question 1

At what week in development do limb buds form?

Answer 1

Week 4

Question 2

At what week in development are the digits fully formed?

Answer 2

Week 8

Question 3

Limbs are formed from muscle, cartilage, and connective tissue. What are the germ layers each of these are derived from?

Answer 3

Muscles = Somite mesoderm (Myotome – Hypomere)

Cartilage (including bone) = Somatic layer of lateral plate mesoderm

CT = Somatic layer of lateral plate mesoderm

***Remember somites come from Paraxial Mesoderm!

Question 4

This structure is a mix of Somites (hypomere) and somatic layer of the lateral plate mesoderm. It produces FGF-10.

Answer 4

Limb-forming mesoderm

Question 5

What signal does Limb-forming Mesoderm give off?

Answer 5

FGF-10

Question 6

When Limb-forming Mesoderm signals FGF-10, what is formed?

Answer 6

Apical Ectodermal Ridge (AER)

***Made from Surface Ectoderm and is what gives us limb-bud ectoderm

Question 7

T/F. As the AER grows out distally, the limb-bud mesoderm (beneath) gives off different signals. These signals turn on genetic programs that make certain cells already know what bones they’re going to become.

Answer 7

True

Question 8

Limbs develop proximodistally. First the ________ is formed, which creates the Humerus and Femur.

Answer 8

Stylopod

Question 9

Limbs develop proximodistally. Second the ________ is formed, which creates the Radius/Ulna and Tibia/Fibula.

Answer 9

Zeugopod

***Distal to Stylopod

Question 10

Limbs develop proximodistally. Third the ________ is formed, which creates the Carpels, Metacarpals, Digits, and Tarsals, Metatarsals, and Digits.

Answer 10

Autopod

***Distal to Zeugopod

Question 11

At what week in development do the hand and foot plates form and the chondrification centers appear?

Answer 11

Week 5

Question 12

At what week in development is the entire limb skeleton cartilaginous and the digital rays of the hands form?

Answer 12

Week 6

Question 13

At what week in development does the digital rays of the feet form, rotation of limbs, and osteogenesis of long bones begin?

Answer 13

Week 7

Question 14

During weeks 6 and 7 the digital rays of hands and feet form because…

Answer 14

Mesenchymal cells condense to form digits

***Embryologic stem cells – mesoderm

Question 15

During week 8, individual digits are formed due to apoptosis which kills the skin cells that are webbed between fingers and toes. This apoptosis is controlled by what signal?

Answer 15

BMPs

Question 16

Limb musculature is derived from dorsolateral cells of the ________.

Answer 16

Somites

Question 17

Motor axons from spinal cord enter the limb buds during the ______ week (neuroectoderm).

Answer 17

5th

Question 18

Sensory axons follow the motor axons and use them for guidance. Sensory axons are from which germ layer?

Answer 18

Neural Crest

Question 19

Neural crest cells become what type of cell for myelination (in PNS)?

Answer 19

Schwann Cells

Question 20

At week 7 limbs undergo rotation. How do the upper limbs rotate and how do the lower limbs rotate?

Answer 20

Upper limbs rotate 90 degrees laterally

Lower limbs rotate 90 degrees medially

Question 21

Explain why the upper limbs develop before the lower limbs?

Answer 21

Due to blood supply. We like to shunt more blood and oxygen to the brain and on the way there is the Subclavian As. which take more blood to the upper extremity.

Question 22

In development, this branches off the dorsal aorta.

Answer 22

Intersegmental Arteries

Question 23

This comes off the Intersegmental Arteries and forms the Brachial A. and Median A. during development.

Answer 23

Primary Axial A.

***Median A. isn’t present in adults, there is remodeling

Question 24

What does the Primary Axial A. give rise to that is important for the upper limb?

Answer 24

Brachial A.

Question 25

What does the Primary Axial A. become for the lower limb?

Answer 25

Deep artery of the thigh

Question 26

How does proximodistal growth occur with the limb bud mesoderm and the AER?

Answer 26

The limb-bud mesoderm signals FGF-10 to form the AER. The AER then in turn will signal FGF-4 and FGF-8 back to the mesenchyme (mesoderm). This constant signaling causes the proximodistal growth to occur.

Question 27

For Dorso-ventral patterning, the dorsal surface is forming the extensors and maintained by _______, while the ventral surface is forming the flexors and is maintained by _______.

Answer 27

Wnt7 | BMPs

Question 28

Anterior-Posterior patterning (also known as Preaxial-Postaxial patterning) is established by what?

Answer 28

Zone of Polarizing Activity (ZPA) ***On posterior side of limb (little finger side)

Question 29

What are the signals from the ZPA that specifically signal the posterior elements to form (3rd, 4th, 5th digits and ulna)?

Answer 29

SHH | Retinoic Acid

Question 30

What would have to be lost to result in the loss of posterior elements (3rd, 4th, 5th digits and ulna)?

Answer 30

Loss of ZPA

Question 31

What would occur in an upregulation of ZPA?

Answer 31

Additional posterior elements (polydactyly)

Question 32

What would occur in a duplication of the ZPA?

Answer 32

Duplication of posterior elements (i.e., Little fingers on both sides of the thumbs)

Question 33

T/F. Anterior elements (i.e., Radius/Thumb) are formed prior to Posterior elements (i.e., little finger/Ulna).

Answer 33

False. The Posterior elements are formed prior to the Anterior elements. ***Therefore, disruption of the Anterior-Posterior patterning growth can result in the loss of anterior elements (i.e., loss of radius and/or thumb)

Question 34

During what week would a birth defect in the hands with upregulation of the ZPA occur (polydactyly)?

Answer 34

Week 6 -- because this is when your forming digital rays of hands

Question 35

During what week would a birth defect in the feet with duplication of the ZPA occur (polydactyly)?

Answer 35

Week 7 -- because this is when your forming digital rays of feet

Question 36

What causes syndactyly (fused fingers)?

Answer 36

Loss/not enough apoptosis of skin between fingers, which means there is a problem with the BMPs ***Remember syndactyly is common with Poland Syndrome!

Question 37

During what week would the birth defect of syndactyly occur?

Answer 37

Week 8 -- because this is when BMPs activate apoptosis of the skin between fingers to form separate digits

Question 38

This is the term for the birth defect that occurs when part of a limb is missing.

Answer 38

Meromelia

Question 39

This is the term for the birth defect that occurs when hands and/or feet are attached close to the body.

Answer 39

Phocomelia

Question 40

Why does Phocomelia occur and in what week?

Answer 40

There is a problem with FGF signaling in the AER, making the Proximo-Distal patterning mess up. Can occur in weeks 4-8

Question 41

This is the term for when upper limbs do not form at all.

Answer 41

Amelia

Question 42

Why does Amelia occur and in what week?

Answer 42

There is a problem with FGF signaling in the AER, making the Proximo-Distal patterning mess up. Occurs in week 4 (very start of limb bud formation)

Question 43

Forked/Split Hand or Foot, also called _________, can occur during week _____ for the hand and week ______ for the foot.

Answer 43

Ectrodactyly 6 7

Question 44

Why does Ecrtodactyly occur?

Answer 44

The center of the AER did not develop properly or it degenerated.

Question 45

This drug was given to expectant mothers to help with morning sickness, but it was found to cause severe limb deformities in their babies.

Answer 45

Thalidomide

Question 46

This is the term for congenital joint contractors, that usually involves more than 1 joint. The causes are unclear, but thought to be due to: - - Neurological defects - - Muscular abnormalities - - Joint and contiguous tissue problems - - Fetal crowding

Answer 46

Arthrogryposis