Limb Development

Question 1

When do the limb buds first appear?

Answer 1

Around the end of the 4th week of development

Question 2

Where does all limb tissue arise from?

Answer 2

Lateral plate mesoderm

Question 3

What determines where on the body the limb develops?

Answer 3

HOX genes

Question 4

Limb bud outgrowth is initiated and maintained by what? For the forelimb? Hindlimb?

Answer 4

Positive feedback loop of FGF10. Transcription factors control the expression of FGF10. Tbx5 in the forelimb and Tbx4 in the hindlimb

Question 5

What is the pathway that initiates the FGF10 positive feedback loop?

Answer 5

Wnt3 –> β-catenin –> Tbx5 –> FGF10 –>FGF8 (positive feedback between FGF10 and FGF8)

Question 6

What is the AER?

Answer 6

The apical ectodermal ridge is a condensation of ectoderm

Question 7

At the AER, what is expressed in the ventral and dorsal ectoderm?

Answer 7

Dorsal: Wnt-7a
Ventral: Engrailed-1

Question 8

Wnt3 initiates the outgrowth of the limb. What is responsible for continuing that growth?

Answer 8

AER

Question 9

What is the progress zone?

Answer 9

Where cells proliferate

Question 10

What is the ZPA?

Answer 10

The zone of polarizing activity. Secretes sonic hedgehog (SHH)

Question 11

What is amelia and what does it result from?

Answer 11

Lack of limbs. Mutation in Wnt3

Question 12

What is diplopodia and what does it result from?

Answer 12

Multiple feet. Duplication of the AER

Question 13

What is archeiropodia and what does it result from?

Answer 13

Bilateral congenital amputations of the upper and lower extremities and aplasia of the hands. Lack of SHH production from the ZPA

Question 14

What is polydactyly and what does it result from?

Answer 14

Supernumerary fingers or toes. Duplication of the ZPA

Question 15

What are the two models for limb patterning?

Answer 15

Progress zone model: the stylopod, zeugopod, and autopod develop over time

Early specification model: the stylopod, zeugopod, and autopod are all present at initiation of limb growth

Question 16

What are the cartilaginous anlage made of?

Answer 16

Type II collagen, type I collagen, fibronectin

Question 17

How are the digits defined?

Answer 17

Interdigital apoptosis

Question 18

What is syndactyly and how does it arise?

Answer 18

Fusion of adjacent fingers. Failure of interdigital apoptosis

Question 19

What initiates joint formation?

Answer 19

Wnt14

Question 20

What are the stages of bone and cartilage development in the limb?

Answer 20

1) bone collar stage
2) periosteal invasion
3) primary ossification center
4) creation of epiphyseal growth plate
5) secondary ossification center

Question 21

How are apophyses formed?

Answer 21

The attachment of muscle and the force enacted on that portion of bone

Question 22

Which bones take the longest to fuse their epiphyseal growth plates?

Answer 22

Sacrum, clavicle

Question 23

What is brachydactyly and how does it arise?

Answer 23

Abnormal shortening of the fingers and toes. Premature closure of the epiphyseal growth plate

Question 24

What kind of myoblasts migrate from the dermomyotome into the limb?

Answer 24

PAX3 positive cells

Question 25

How do limb myoblasts migrate into the limb (in comparison to the body wall)?

Answer 25

As mesenchymal condensations

Question 26

Where do the tendon precursors come from?

Answer 26

Scx-expressing cells

Question 27

What signals ridge formation on skeletal elements that will eventually become the bony landmarks?

Answer 27

tendon cells, utilizing FGF and TGFβ

Question 28

What is vasculogenesis?

Answer 28

De novo formation of blood vessels

Question 29

What is angiogenesis?

Answer 29

Remodeling of preexisting vessels