Development of Limbs

Question 1

when do limb buds begin to appear

Answer 1

week 4

Question 2

when do digits begin to appear

Answer 2

week 8

Question 3

when does the 1st ossification occur

Answer 3

week 12

Question 4

which limbs develop first: upper or lower

- why

Answer 4

upper

- blood is being pumped to the head for development; upper limb is closer to head

Question 5

how does development of the limbs proceed

Answer 5

proximodistally

Question 6

where does the muscle of the limbs originate from

Answer 6

paraxial mesoderm –> somite –> myotome –> hypomere –> hypaxial muscles

Question 7

where do the cartilage and connective tissue of the limbs originate from

Answer 7

somatic layer of the lateral plate

Question 8

what does the limb forming mesoderm release to stimulate the surface ectoderm to become to the apical ectodermal ridge

Answer 8

FGF-10

Question 9

what does FGF-10 do

Answer 9

stimulates surface ectoderm to become the apical ectodermal ridge

Question 10

what is the apical ectodermal ridge and what is it needed for

Answer 10

• thickening of the surface ectoderm

- needed for limb development

Question 11

what does the apical ectodermal ridge release to stimulate limb mesoderm

Answer 11

FGF-8 and FGF-4

Question 12

what does the release of FGF-8 and FGF-4 from the apical ectodermal ridge do

Answer 12

stimulates limb mesoderm which then proliferates and migrates to facilitate proximodistal development of the limbs

Question 13

what is the most proximal region of the limb buds and what does it develop into in the upper limb

Answer 13

Stylopod region

- humerus, femur

Question 14

what is the middle region of the limb buds and what does it develop into in the upper limb

Answer 14

Zeugopod

- radius/ulna and tibia/fibula

Question 15

what is the most distal region of the limb buds and what does it develop into in the upper limb

Answer 15

Autopod

- carpals, metacarpals, digits, tarsals, metatarsals

Question 16

when do the hand and foot plates develop as well as the chondrification centers

Answer 16

week 5

Question 17

when do the digital rays of hands develop

Answer 17

week 6

Question 18

what condenses to make bones for the digits in week 6

Answer 18

somatic lateral plate

Question 19

at week 6 what is the entire limb skeleton made of

Answer 19

cartilage

Question 20

when do the digital rays of the feet, rotation of the limbs, and osteogenesis of long bones begin

Answer 20

week 7

Question 21

which develops first: hand plates or foot plates?

Answer 21

hand plates

Question 22

when does separation of digits and apoptosis occur?

Answer 22

week 8

Question 23

what is apoptosis due to in week 8

Answer 23

BMP

Question 24

when do motor axons from the spinal cord enter the limb buds

Answer 24

week 5

Question 25

Name the specific myotomes for where: - the upper limbs develop - the lower limbs develop

Answer 25

upper limbs: cervical myotomes | lower limbs: lumbar and sacral myotomes

Question 26

what rotations occur in the limbs at week 7 | - where do the elbows and knees now point

Answer 26

upper limbs rotate 90 degrees laterally lower limbs rotate 90 degrees medially - the elbows now point caudally and the knees point cranially

Question 27

what artery does the primary axial artery become in the upper limbs

Answer 27

brachial artery

Question 28

what artery does the primary axial artery become in the lower limbs

Answer 28

deep artery of the thigh

Question 29

what occurs to remodel arterial supply in the limbs

Answer 29

angiogenesis

Question 30

Club Foot (talipes Equinovarus)

Answer 30

- sole of foot is turned medially and inverted - all anatomical structures are present - 2x more frequent in males

Question 31

Potential causes of Club Foot

Answer 31

not enough amniotic fluid so limbs cannot rotate properly

Question 32

Developmental Hip Displasia

Answer 32

- underdevelopment of acetabulum in the hip bone (hip joint socket)

Question 33

what do Hox genes regulate in limb development

Answer 33

- positioning of the limbs along the craniocaudal axis in proximo-distal growth - regulate types and shapes of bones

Question 34

what do things are needed for proximo-distal patterning

Answer 34

Apical ectodermal ridge (AER) | HOX genes

Question 35

what maintains the dorsal surface in dorso-ventral patterning

Answer 35

Wnt7

Question 36

what maintains the ventral surface in dorso-ventral patterning

Answer 36

BMPs

Question 37

what do Wnt7 and BMP set up in patterning growth

Answer 37

the apical ectodermal ridge (AER)

Question 38

what establishes the anterior-posterior patterning

Answer 38

Zone of Polarizing Activity (ZPA)

Question 39

how does ZPA signal posterior elements | - what are the posterior elements

Answer 39

SHH and retinoic acid signaling | - digits 3-5 and ulna

Question 40

loss of ZPA results in

Answer 40

loss of posterior elements | - ex: 4th digit, 5th digit, ulna

Question 41

up-regulation of ZPA results in

Answer 41

additional posterior elements | - ex: polydactyly

Question 42

duplication of ZPA results in

Answer 42

duplication of posterior elements - ex: little fingers on both sides of the thumb - ex: second set of toes

Question 43

why can disruption of AP patterning and growth result in loss of anterior elements

Answer 43

posterior elements are formed prior to anterior elements

Question 44

Meromelia | - when does the defect occur

Answer 44

results in a shrunken and deformed extremity | - defect occurs in weeks 3-5 in development

Question 45

Phocomilia

Answer 45

shortened hands and legs

Question 46

what prescribed drug used to cause meromelia

Answer 46

Thalidomide

Question 47

brachydactyly - how is it caused - when

Answer 47

shortened digits | - FGF-8, 10, and 4 disruption in weeks 6-8

Question 48

syndactyly - how is it caused - when

Answer 48

webbing of the digits | - down-regulation of BMPs needed for apoptosis in week 8

Question 49

Amelia - what is it - when

Answer 49

missing both upper limbs | - weeks 3 and 4

Question 50

Ectrodactyly - "Lobster Claw" - what causes it - when

Answer 50

apical ectodermal ridge was down-regulated and the digits did not form - week 6 for hand and week 7 for feet

Question 51

Arthrogryposis

Answer 51

congenital joint contractures | - causes unclear