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MSK Exam 1 > Limb Development > Flashcards

Limb Development Flashcards

1
Q

When does the upper limb form?

A

Day 24

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2
Q

When does the lower limb form?

A

Day 25-26

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3
Q

Mesenchymal cells grow out from what section of mesoderm?

A

Lateral Plate Mesoderm

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4
Q

Limb buds form deep to a thick band of ectoderm called the:

A

Apical Ectodermal Ridge (AER)

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5
Q

Regions of the limb bud consists of:

A
  • Stylopod: humerus, femur
  • Zeugopod: radius & ulna, tibia & fibula
  • Autopod: carpals, metacarpals, phalanges; tarsals, metatarsals, phalanges
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6
Q

What are the 3 axes of the limb bud?

A
  • Proximal - Distal (shoulder -> digits)
  • Cranial - Caudal (Hallux -> Phalanx V)
  • Dorsal - Ventral (Dorsum -> Palm)
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7
Q

Apical Ectodermal Ridge

A
  • Specialized, multilayered epithelial structure located along the ridge of each limb
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8
Q

What induces the AER?

A

FGF10 (produced by the mesodermal band)

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9
Q

Limb consists of:

A
  • Mesoderm/mesenchyme core
  • AER at top of limb bud
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10
Q

What does AER secrete?

A

FGF8

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11
Q

___ feedback loop between FGF8 and FGF10

A

Positive

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12
Q

What type of signaling is essential for the initiation of limb development and regulates the outgrowth of the proximodistal axis?

A

FGF

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13
Q

Complete/early removal of AER (or FGF8) results in:

A

Arrested limb development (if removed early enough then limb will be completely absent)

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14
Q

Removal of AER (of FGF8) at later stages results in:

A

Loss of more distal elemtents

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15
Q

Transplanting an AER (or adding FGF8) can result in:

A

Supernumerary limbs (new limb bud/extra limbs)

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16
Q

List the 8 Limb Anomalies

A
  • Meromelia
  • Amelia
  • Phocomelia
  • Adactyly
  • Ectrodactyly
  • Polydactyly
  • Brachydactyly
  • Syndactyly
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17
Q

Meromelia

A
  • Absence of part of a limb
  • Intermediate to late loss of FGF (protein) signaling
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18
Q

Amelia

A
  • Absence of entire limb
  • Early loss of FGF signaling
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19
Q

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 thalidomide exposure during prenatal development
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20
Q

Adactyly

A
  • Absence of digits
  • Late loss of FGF signaling
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21
Q

Ectrodactyly

A
  • Split hand or split foot anomaly
  • “Lobster claw” deformity
  • Partial absence of FGF8 from AER
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22
Q

Cranial-caudal axis is patterned by the:

A

Zone of Polarizing Activity

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23
Q

SHH patterning across digits

A
  • Digit 1: SHH independent
  • Digit 2: Paracrine SHH signaling (concentration and diffusion)
  • Digit 3: Autocrine/paracrine SHH signaling (time of expression and concentration)
  • Digits 4 & 5: Autocrine SHH signaling (time of expression)
24
Q

Where is the ZPA located?

A

At the caudal base of the limb bud near future digit 5

25
Q

What regulates the cranial-caudal axis?

A

SHH signaling from ZPA

26
Q

What signaling molecule is expressed in the ZPA and is sufficient to provide ZPA function?

A

SHH

27
Q

What happens if ZPA is grafted to cranial limb bud mesoderm (implant SHH producing fibroblasts into the anterior portion of the limb bud)?

A

Duplicated (mirrored) digits emerge

28
Q

What happens if there is an over-expression of SHH in limb development?

A

Polydactyly because it establishes a second Zone of polarizing activity and thus more digits than normal

29
Q

What gene regulates the cranial-caudal and proximodistal axes?

A

Hox genes

30
Q

What Hox genes are expressed within the scapula?

A

Hox9

31
Q

What Hox genes are expressed within the arm (humerus)?

A

Hox9 & Hox10

32
Q

What Hox genes are expressed within the ulna, radius, and proximal carpals?

A

Hox9, Hox10, & Hox 11

33
Q

What Hox genes are expressed within the distal carpals?

A

Hox9, Hox10, Hox11 & Hox12

34
Q

What Hox genes are expressed within the metacarpals and phalanges?

A

Hox9, Hox10, Hox11, Hox12 & Hox13

35
Q

Hox9-10 paralogs specify:

A

Stylopod

36
Q

Hox11 paralogs specify:

A

Zeugopod

37
Q

Hox12-13 paralogs specify:

A

Autopod

38
Q

Brachydactyly

A
  • Shortening of the fingers and toes due to unusually short bones
  • Genetic changes in the HOXD13 gene or PTHLH gene (parathyroid like hormone)
  • Autosomal dominant inheritance
39
Q

What signaling molecule is expressed in the dorsal ectoderm and is a primary regulatory of dorsal fates?

A

Wnt7a

40
Q

Overexpression of Wnt7a results in:

A

Dorsalized structures

41
Q

Wnt7a KO mice have ___ paws

A

Ventralized paws (foot pads form on dorsal surface)

42
Q

What signaling molecule is expressed in the ventral ectoderm?

A

En1

43
Q

What are the functions of En1?

A
  • Prevents expression of Wnt7a in the ventral part of the limb
  • Restricts positioning of the AER to establish the dorsal-ventral axis
44
Q

Removal of interdigital mesenchyme involves?

A
  • Apoptosis of interdigital mesenchyme which frees the digits and allows mobility
  • Requires BMP signaling
45
Q

If high levels of BMP signaling:

A

Increased cell death

46
Q

If low levels of BMP signaling:

A

Decreased cell death (webbing of digits)

47
Q

When do digital rays form in the hand plates? Foot plates?

A
  • By the 6th week
  • By the 7th week
48
Q

What week of development do separate digits form?

A

8th week

49
Q

Syndactyly

A
  • Fusion of digits because digital rays rail to develop
  • two types:
    (1) Cutaneous Syndactyly: webbing between digits due to failure to degenerate cutaneous elements; disruption in BMP signaling, lack of apoptosis
    (2) Osseous Syndactyly: fusion of bones (synostosis) due to failure of notches to develop between digital rays; autosomal dominant; HoxD13 mutation
50
Q

Dorsal muscle mass forms:

A
  • Extensors and supinators of upper limb
  • Extensos and abductors of lower limb
51
Q

Ventral muscle mass forms:

A
  • Flexors and pronators of upper limb
  • Flexors and adductors of lower limb
52
Q

What arises from the somatic layer of lateral plate mesoderm?

A

Limb tendons

53
Q

When does limb innervation begin?

A

5th week

54
Q

What two branches does a spinal nerve branch into after exiting the spinal cord?

A

(1) Dorsal ramus -> Epimere
(2) Ventral ramus -. Hypomere & limbs

55
Q

Do motor or sensory neurons innervate first?

A

Motor neurons

56
Q

Muscles originating in the dorsal muscle mass are innervated by dorsal branches of the:

A

Ventral Rami

57
Q

Muscles originating in the ventral muscle mass are innervated by ventral branches of the:

A

Ventral Rami

MSK Exam 1 (6 decks)

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