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MSK Exam I > Limb Development > Flashcards

Limb Development Flashcards

1
Q

What does the musculature arise from?

A

Myotome of the paraxial mesoderm

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2
Q

What do bones arise from?

A

From somatic layer of lateral plate mesoderm

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3
Q

What do tendons arise from?

A

From somatic layer of lateral plate mesoderm

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4
Q

When do the upper limbs form?

A

24 days

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5
Q

When do the lower limbs form?

A

25-26 days

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6
Q

Limb buds form deep to what structure?

A

A thick band of ectoderm known as the apical ectodermal ridge (AER)

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7
Q

What causes the limb bud to bulge outward?

A

Proliferation and outgrowth of mesenchyme from the later plate mesoderm

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8
Q

What are the three regions of outgrowth in a limb bud?

A

Stylopod, zeugopod and autopod

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9
Q

What does the stylopod form?

A

Humerus or femur

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10
Q

What does the zeugopod form?

A

Radius and ulna + tibia and fibula

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11
Q

What does the autopod form?

A

Carpals, metacarpals, and phalanges

Tarsals, metatarsals and phalanges

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12
Q

What are the three axes of the limb bud?

A 
Proximal distal (shoulder to digits) 
Cranial caudal 
Dorsal ventral (dorsum to palm)
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13
Q

What is the AER and where is it located?

A

It is a specialized multilayered epithelial structure located along the ridge of each limb bud

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14
Q

What induces the AER?

A

FGF10

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15
Q

What is secreted by AER?

A

FGF8

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16
Q

Describe the positive feedback loop of FGF8 and 10

A

FGF8 is secreted by the AER and stimulates its down stream target FGF10
FGF10 then in turn stimulates AER to produce more FGF8

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17
Q

What is FGF signaling essential for?

A

The initiation of limb development and regulates the outgrowth of the proximodistal axis

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18
Q

What happens if you completely remove the AER?

A

Arrests limb development

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19
Q

What happens if the AER is removed at later stages of development?

A

Loss of more distal elements occurs

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20
Q

What occurs when transplanting an AER?

A

Can result in supernumerary limbs

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21
Q

What is the cranial caudal axis patterned by?

A

The zone of polarizing activity (ZPA)

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22
Q

When does restriction of cell fates in the limb bud occur?

A

Before limb bud outgrowth

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23
Q

What signaling factor is expressed in the ZPA and is sufficient for its function?

A

Shh

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24
Q

What is the result when the ZPA is grafted to cranial limb bud mesoderm?

A

Duplicated digits emerge (mirrored)

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25
Q

What is polydactyly?

A

Presence of supernumerary digits
Inherited as a dominant trait
Overexpression of Shh establishes the second ZPA
Extra digit is incompletely formed and lacks normal muscular development

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26
Q

What are Hox genes?

A

Paralogs that regulate development and regulate the cranial caudal and proximodistal axes

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27
Q

Hox9-10 paralogs specify what?

A

Stylopod

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28
Q

Hox11 paralogs specify what?

A

Zeugopod

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29
Q

Hox12-13 paralogs specify what?

A

Autopod

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30
Q

Expression of HoxD genes can be correlated with what?

A

Development of specific elements of the forelimb skeleton

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31
Q

Hoxd9 is within what structure?

A

Scapula

32
Q

Hoxd9-10 are within what structure?

A

Arm (humerus)

33
Q

Hoxd9-11 are within which structures?

A

Ulna, radius and proximal carpals

34
Q

Hoxd9-12 are within which structure?

A

Distal carpals

35
Q

Hoxd9-13 are within which structures?

A

Metacarpals and phalanges

36
Q

What is brachydactyly?

A

Shortening of the fibers and toes due to unusually short bones
Genetic changes in the HoxD13 gene of PTHLH
If inherited occurs as autosomal dominant

37
Q

What is Wnt7a and where is it expressed?

A

It is expressed in the dorsal ectoderm and is a primary regulator of dorsal fates

38
Q

What happens when Wnt7a is overexpressed?

A

Results in dorsalized strucutres

39
Q

Wnt7a KO mice have what?

A

Ventralized paws (foot pads form on dorsal surface)

40
Q

Where is Engrailed (En1) expressed?

A

In the ventral ectoderm

41
Q

What is the function of engrailed?

A

Prevents the expression of Wnt7a in the ventral part of the limb
En1 also restricts positioning of the AER to establish the dorsal ventral axis

42
Q

Which two signaling factors are important for development of the dorsal ventral axis?

A

Wnt7a and engrailed

43
Q

Describe formation of the digits

A

Removal of interdigital mesenchyme frees the digits and allows mobility
Involves apoptosis and requires BMP signaling

44
Q

An increase in BMP signaling results in what?

A

Increase cell death allowing for freeing of the digits

45
Q

A decrease in BMP signaling results in what?

A

Decreased cell death (resulting in webbed digits)

46
Q

When do digital rays in the hand plate form?

A

By 6th week

47
Q

When do digital rays in the foot plates form?

A

By the 7th week

48
Q

When are separate digits formed?

A

By the 8th week

49
Q

Describe development of the limb musculature

A

Myogenic precursors from the dermomyotome of the paraxial mesoderm migrate into the limb bud —> differentiate into myoblasts —> aggregate and form dorsal and ventral muscle masses in each limb bud

50
Q

What does the dorsal muscle mass form?

A

Extensors and supinators of upper limb + extensors and abductors of lower limb

51
Q

What does the ventral muscle mass form?

A

Flexors and pronators of upper limb + flexors and adductors of lower limb

52
Q

When does limb innervation begin?

A

In the 5th week

53
Q

What happens are spinal nerves exit the spinal cord?

A

They split into two branches - dorsal and ventral ramus

54
Q

What does the dorsal ramus innervate?

A

Epimere

55
Q

What does the ventral ramus innervate?

A

Hypomere and limbs

56
Q

Muscles originating in dorsal muscle mass are innervated by what?

A

Dorsal branches of ventral rami

57
Q

Muscles originating in the ventral muscle mass are innervated by what?

A

Ventral branches of ventral rami

58
Q

What provides blood supply to the limbs?

A

Branches of the intersegmental arteries (arising from the dorsal aorta)

59
Q

Describe the vascular development in the upper limb

A

Primary axial artery—> brachial and common interosseous artery —> radial and ulnar arteries (terminal branches)

60
Q

The primordial vascular pattern consists of what?

A

A primary axial artery and its branches

61
Q

Describe the vascular development in the lower limb

A

Primary axial artery —> deep artery of thigh and anterior and posterior tibial arteries

62
Q

Describe the venous supply of the developing limbs

A

Primary axial artery drains into marginal sinus —> then drains into singular peripheral vein —> marginal sinus breaks up —> basilic and cephalic veins develop

63
Q

How is the limb bud initially oriented?

A

With the ventral surface facing medially and the dorsal surface facing laterally
Both are continuous with the ventral and dorsal surfaces of the embryonic trunk

64
Q

Describe upper extremity rotation

A

Rotates 90 degrees laterally
Flexor = anterior
Extensor = posterior

65
Q

Describe LE rotation

A

Rotates 90 degrees medially
Flexors = posterior
Extensors = anterior

66
Q

What is meromelia?

A

Absence of part of a limb

Intermediate to late loss of FGF signaling

67
Q

What is Amelia?

A

Absence of entire limb

Early loss of FGF signaling

68
Q

What is phocomelia?

A

Loss of long bones with hands and/or feet attached close to the body
Partial loss of FGF signaling or Hox disruption due to thalomide

69
Q

What is adactyly?

A

Absence of digits

70
Q

What is syndactyly?

A

Fusion of digits because digital rays fail to develop

Two types: cutaneous and osseous

71
Q

What is cutaneous syndactyly?

A

Webbing between digits due to failure to degenerate likely due to a disruption in BMP signaling (lack of apoptosis)

72
Q

What is osseous syndactyly?

A

Fusion of bones (synostosis) due to failure of notches to develop between digital rays
Inherited as an autosomal dominant Hoxd13 mutation

73
Q

What is erodactyly?

A

Split hands or split foot anomaly (lobster claw deformity)
Partial absence of FGF8 from AER
Also known as ectodermal dysplasia-cleft lip/palate syndrome (EEC)

74
Q

What are amniotic bands?

A

Adhesions between amnion and affected fetal structures

75
Q

What is bilateral talipes equinovarus?

A

Club foot

Oligohydramnios reduces fetal movements

76
Q

Describe the timeline of limb development

A

4th week: both limb buds present
5th week: hand/foot plates appear and chondrification begins
6th week: digital rays of hands, limb skeleton is cartilaginous
7th week: digital rays of feet, osteogenesis begins, rotation of limbs occur
8th week: separate digits are formed
12th week: primary ossification begins

MSK Exam I (34 decks)

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