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MSK Exam II > Limb Development > Flashcards

Limb Development Flashcards

1
Q

Musculature is derived from what embryonic precursor?

A

Paraxial mesoderm –> somite –> myotome

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2
Q

Bones are derived from what embryonic precursor?

A

Lateral plate mesoderm –> somatic region

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3
Q

Tendons are derived from what embryonic precursor?

A

Lateral plate mesoderm –> somatic region

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4
Q

By what week of development are both limb buds present?

A

Week 4

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5
Q

By what week in development does primary ossification of the limbs begin?

A

Week 12

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6
Q

By what week in development do hand/foot plates appear and chondrification begins?

A

Week 5

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7
Q

By what week in development does the embryo begin showing separation of digits?

A

8th week

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8
Q

By what week in development do digital rays of feet appear, osteogenesis begins, and rotation of limbs occurs?

A

7th week

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9
Q

By what week of development do digital rays of hands appear and limb skeleton is cartilaginous?

A

6th week

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10
Q

Which limbs form first, upper or lower?

A

Upper limb buds form at 24 days

Lower limb buds form at 28 days

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11
Q

Limb bud formation is due to proliferation of __________ cells from ______ ______ mesoderm (somatic region)

This causes the limb bud to bulge outward

A

Mesenchymal; lateral plate

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12
Q

What are the 3 axes of the limb buds?

A

Proximal/distal

Cranial/caudal

Dorsal/ventral

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13
Q

What structures are associated with the proximal/distal axis of the upper limb bud?

A

Shoulder = proximal

Digits = distal

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14
Q

What structures are associated with the cranial/caudal axis of the upper limb bud?

A

Cranial = hallux

Caudal = phalanx 5

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15
Q

What structures are associated with the dorsal/ventral axis of the upper limb bud?

A

Dorsal = dorsum of hand

Ventral = palm of hand

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16
Q

What is the stylopod as it refers to limb structure?

A

Humerus or femur

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17
Q

What is the zeugopod as it relates to limb structure?

A

Radius + ulna; tibia + fibula

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18
Q

What is the autopod as it relates to limb structure?

A

Hand; foot

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19
Q

What molecular interaction is resposible for initiating limb bud outgrowth?

A

Fgf10 from mesenchyme (lateral plate mesoderm) activates Wnt signaling

Wnt then induces Fgfs in the ectoderm - this is a positive feedback loop

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20
Q

What region of the limb bud controls proximal-distal outgrowth of the limb?

A

Apical Ectodermal Ridge (AER)

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21
Q

What does the AER secrete that allows for continued limb outgrowth?

A

Fgf8

[Fgf soaked beads induce supernumerary limbs; Fgfs can mimic the functions of the AER itself]

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22
Q

What would be the result of experimental removal of the AER?

A

Limb development ceases

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23
Q

What would be the result of experimental addition of AER material?

A

Wing/limb is duplicated

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24
Q

What would be the result of experimental replacement of upper limb mesenchyme with lower limb mesenchyme?

A

Leg develops in place of arm

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25
Q

What would be the result of experimental replacement of limb mesenchyme with nonlimb mesenchyme?

A

AER regresses; limb development ceases

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26
Q

What would be the result of AER replacement by FGF bead?

A

Wing/limb develops normally

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27
Q

The AER is responsible for limb outgrowth, but not limb identity. What gene clusters are expressed in limb buds that correspond to identity of structures?

A

Hox gene clusters

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28
Q

Hox11 paralogs are responsible for formation of what aspect of limb structure?

A

Zeugopod

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29
Q

Hox9-10 paralogs are responsible for formation of what aspect of limb structure?

A

Stylopod

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30
Q

Hox12-13 paralogs are responsible for formation of what aspect of limb structure?

A

Autopod

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31
Q

__________ = genes related to each other due to descent from a common ancestral DNA sequence (commonly duplication)

A

Paralogues

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32
Q

Hox expression pattern correlates with the identity of elements along the __________-________ axis

A

Proximal-distal

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33
Q

________-_______ axis specification is the earliest restriction of cell fates in the limb; it occurs before limb bud outgrowth even begins

A

Anterior-posterior

34
Q

A-P axis specification is the earliest restriction of cell fates in the limb. What is responsible for patterning these cell fates?

A

Zone of polarizing activity (ZPA)

35
Q

A-P axis specification is the earliest restriction of cell fates in the limb. Cell fates are patterned by the zone of polarizing activity (ZPA). What important signaling factor is expressed in the ZPA?

A

Sonic hedgehog (Shh)

36
Q

T/F: SHH is expressed in the ZPA and is sufficient on its own to provide ZPA function

A

True!

When the ZPA is grafted to anterior limb bud mesoderm, duplicated digits emerge

37
Q

What signal factor is the primary regulator of the dorsal-ventral axis of the limb bud?

A

Wnt7a

38
Q

Wnt7a is the primary regulator of the dorsal-ventral limb bud axis.

It is responsible for __________ structures.

Wnt7a knockouts have ________ paws.

It is itself controlled by ________.

A

Dorsalizing

Ventralized

Lmx1b

39
Q

Formation of individual digits occurs through what cellular process?

A

Apoptosis

40
Q

At what day of development does formation of digits via apoptosis begin?

A

Day 48, mostly complete by day 56

41
Q

Formation of digits occurs through apoptosis beginning at day 48 of development. This requires what signaling factor?

A

BMP

[increased BMP –> increased cell death, areas with decreased BMP have decreased cell death - results in webbed digits]

42
Q

Prior to limb rotation, the limbs are oriented with the ventral surfaces (flexors) facing __________, and the dorsal surfaces (extensors) facing __________

A

Medially
Laterally

[both are continueous with the ventral and dorsal surfaces of the embryonic trunk at this point]

43
Q

During which week in development does limb rotation occur?

A

Week 7

44
Q

Rotation of the limbs occurs as torsion in the ________ and _________ diaphysis

A

Femoral; humeral

45
Q

Beginning in week 7 of development, the upper limbs undergo ________ rotation, while the lower limbs rotate _________

A

Lateral; medially

46
Q

Describe the end result of limb rotation in the upper extremity

A

Upper extremity rotates 90 degrees laterally

Flexor compartment faces anteriorly and extensors are posterior

47
Q

Describe the end result of limb rotation in the lower extremity

A

Lower extremity rotates 90 degrees medially

Flexor compartment is posterior and extensors are anterior (this is opposite the upper limb!)

48
Q

What is responsible for the irregular appearance of the dermatomes in the limbs?

A

Limb rotation

49
Q

Limb musculature is derived from the __________ cells of the somites

A

Dorsolateral

50
Q

Is limb musculature derived from epimere or hypomere?

A

Hypomere

51
Q

What do limb tendons arise from?

A

Lateral plate mesoderm

52
Q

The dorsal muscle mass forms what muscles in the upper and lower limbs?

A

Upper limb: extensors and supinators

Lower limb: extensors and abductors

53
Q

The ventral muscle mass forms what muscles in the upper and lower limbs?

A

Upper limb: flexors and pronators

Lower limb: flexors and adductors

54
Q

Bone formation in the limbs is considered endochondral ossification from a ________ cartilage precursor

A

Hyaline

55
Q

T/F: Limb innervation begins with sensory fiber outgrowth first

A

False

Axons within ventral rami (MOTOR) innervate limb muscles during the 5th week

56
Q

Why is it important that motor axons form first?

A

The sensory axons follow the motor axons and use them for guidance

57
Q

Once motor and sensory axons have been established during the process of limb innervation, what is the next step?

A

Neural crest cells form Schwann cells which are responsible for myelination of the newly formed axons

58
Q

A sorting process must occur during the process of limb innervation.

Axons cranial to the limb innervate _________ musculature.

Axons caudal to the limb innervate __________ musculature.

A

Dorsal

Ventrocaudal

59
Q

What are the 2 sources for blood supply to the limbs?

A

Axial artery

Remodeling of branches of 7th cervical intersegmental a. and 5th lumbar intersegmental a.

60
Q

The 2 sources of blood supply to the limbs are the axial a. and the remodeling of branches of the 7th cervical intersegmental a. and the 5th lumbar intersegmental a.

What is the axial a. derived from and describe its length

A

Axial a. develops de novo within the central axis of the limb (by day 30 in the upper limb and day 36 in the lower limb)

It extends the length of the limb

61
Q

The 2 sources of blood supply to the limbs are the axial a. and the remodeling of branches of the 7th cervical intersegmental a. and the 5th lumbar intersegmental a.

Where do the remodeling branches originate, branch, and join?

A

They originate within surrounding mesoderm and join the dorsal aorta

They then branch and join an axial a.

62
Q

The primary blood supply to the upper limb comes from the axial artery. What is the corresponding primary blood supply in the lower limb?

A

Ischiadic a.

63
Q

T/F: Limb anomalies occur in 1:200 live births and typically can be corrected surgically

A

True

64
Q

__________ = limb anomaly characterized by the absence of part of a limb d/t late or partial loss of FGF signaling

A

Meromelia

65
Q

___________ = limb anomaly characterized by absence of an entire limb due to early loss of FGF signaling

A

Amelia

66
Q

__________ = limb anomaly characterized by presence of supernumerary digits, inherited as a dominant trait

A

Polydactyly

67
Q

Polydactyly occurs due to overexpression of _______, which establishes a second ______

A

SHH; ZPA

68
Q

Polydactyly most commonly occurs at which of the following areas?

A. Medial
B. Lateral
C. Dorsal
D. Ventral
E. A and B
A

E. A and B

[note that with the foot specifically, the extra toe is usually on the lateral side]

69
Q

Describe characteristics of extra digits formed in polydactyly

A

Extra digit(s) are usually incompletely formed and lack normal muscular development

70
Q

___________ = limb anomaly characterized by absence of digits

A

Adactyly

71
Q

__________ = limb anomaly characterized by fusion of digits

A

Syndactyly

72
Q

Syndactyly is characterized by the fusion of digits. What are the 2 types of syndactyly?

A

Cutaneous syndactyly

Osseous syndactyly

73
Q

What type of syndactyly is characterized by the fusion of bones (synostosis)?

A

Osseous syndactyly

74
Q

What type of syndactyly is characterized by simple webbing between digits due to failure of apoptosis to degenerate this webbing?

A

Cutaneous syndactyly

75
Q

Syndactyly may occur if _______ ______ fail to develop.

It is inherited as a simple _______ _______ trait.

May occur due to ______ disruption or _______ mutation.

A

Digital rays

Autosomal dominat

BMP; HoxD13

76
Q

_________ is a limb anomaly characterized by absence of long bones, with rudimentary hands and feet due to partial loss of FGF signaling or Hox disruption

A

Phacomelia

77
Q

____________ is a non-genetic cause of limb anomalies as it is a drug that was used as a sedative and anti-nauseant in pregnant women between 1957 and 1962. It is now contraindicated in pregnancy but it continues to be used as a chemotherapy drug for its ability to inhibit angiogenesis.

A

Thalidomide

78
Q

What limb anomaly is also known as split-hand or split-foot anomaly?

A

Ectrodactyly (lobster-claw deformity)

[may be due to a variety of genetic mutations: DLX5/6, P63, FGF8, etc.]

79
Q

_________ ________ = adhesions between amnion and affected fetal structures that may cause limb anomalies

A

Amniotic bands

80
Q

What is the medical term for “club foot”?

A

Talipes equinovarus

81
Q

What condition, characterized by a reduction in amniotic fluid, may reduce fetal movement leading to amniotic bands and/or talipes equinovarus?

A

Oligohydramnios

MSK Exam II (20 decks)

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