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Musculoskeletal/Rheum > Embryo Limb Development > Flashcards

Embryo Limb Development Flashcards

1
Q

where do the muscles of the limbs arise from?

A

Paraxial mesoderm

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2
Q

where do the limbs arise from?

A

somatic mesoderm

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3
Q

what weeks do the limbs form in

A

weeks 4-8

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4
Q

when are the basic structures of limbs (bones and muscle groups) established

A

between weeks 4-8

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5
Q

when do the fingers separate and ossification begins?

A

day 56

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6
Q

what germ layer does the limb bud come from

A

ectoderm and lateral plate (somatic) mesoderm

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7
Q

what germ layer do the bones, tendons, and vasculature come from

A

lateral plate (somatic) mesoderm

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8
Q

what germ layer do the muscles come from

A

paraxial mesoderm

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9
Q

when does the upper limb bud form

A

day 24

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10
Q

when does the lower limb bud form

A

day 28

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11
Q

what are the 3 axes of limb bud formation

A

proximal-distal
cranial-caudal
dorsal-ventral

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12
Q

what is proximal-distal growth controlled by

A

Apical ectodermal ridge (AER)

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13
Q

what is the AER necessary for

A

limb outgrowth

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14
Q

what is the AER sufficient for

A

Limb outgrowth

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15
Q

what is significant about removal of the AER at later stages

A

loss in more distal elements, less severe

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16
Q

what is significant about removal of the AER at earlier stages

A

more severe loss of limb development

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17
Q

what are fibroblast growth factors (FGFs)

A

large family of proteins that are secreted by other cells

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18
Q

what can FGFs mimic

A

the function of the AER

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19
Q

what can proximal-distal outgrowth be rescued by

A

replacing the AER with FGF-coated beads because FGF coated beads can induce supernumerary limbs

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20
Q

Explain model for proximal-distal axis specification

A

Fgf8 stimulates fgf10 and allows it to proliferate. Fgf10 stimulated fgf8 and allows it to proliferate. constant loop. Reciprocal secretion; if cut off, arrest in limb formation

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21
Q

what is the proximal-distal axis comprised of in the genome

A

hox gene clusters A-D

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22
Q

what is the significance of hox gene expression

A

hox gene expression pattern correlates with identity of elements along the proximal-distal axis

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23
Q

what is Hox 9 associated with

A

important in the development of all parts of limb

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24
Q

what is Hox 10 gene associated with

A

stylopod, zeugopod, and autopod, and phalanx

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25
Q

what is Hox 11 associated with

A

zeugopod, autopod, and phalanx

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26
Q

what is Hox 12 associated with

A

autopod and phalanx

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27
Q

what is Hox 13 associated with

A

phalanx

28
Q

what does each cell have in proximal-distal patterning that tells it it’s fate

A

positional address

29
Q

How is cell fate regulated in limb formation

A

positional address; varying concentration, and spacio-temporal expression patterns of signals (FGFs, Wnts) regulate cell fate specification along prox.-dist. axis

30
Q

what is the significance of the Zone of Polarizing Activity (ZPA)

A

ZPA is sufficient for specification of posterior fate

31
Q

what gene is expressed in the ZPA

A

sonic hedgehog (Shh)

32
Q

what is needed for the formation of fingers and toes

A

apoptosis and bone morphogenic proteins (BMPs)

33
Q

what does an increase in BMP signaling cause

A

increase in cell death; digits freed earlier than should be

34
Q

what does a decrease in BMP signaling cause

A

decrease in cell death; webbed digits

35
Q

what is significant about day 56 in fetal development

A

fingers of the right and left hand overlap along midline. This helps track fetal growth!

36
Q

what occurs in limb rotation (weeks 6-8)

A

upper limbs laterally rotate 90 degrees
lower limbs medially rotate 90 degrees

37
Q

what cells do limb muscles arise from

A

hypomeres (paraxial mesoderm)

38
Q

what does the dorsal muscle mass form

A

extensors and supinators in upper limb
extensors and abductors in lower limb

39
Q

what does the ventral muscle mass form

A

flexors and pronators of the upper limb
flexors and adductors of lower limb

40
Q

where do limb tendons arise from

A

lateral plate mesoderm

41
Q

where do bones arise from

A

lateral plate mesoderm

42
Q

how are bones formed

A
  1. mesenchymal cells condense and differentiate into chondrocytes
  2. hypertrophic chondrocytes secrete VEGF
  3. Blood vessels invade the center bringing in osteoblasts
  4. osteoblasts bind mineralized matrix
  5. at birth, diaphysis (shaft) is completely ossified whereas the epiphysis (end of long bone) is still cartilaginous
  6. at birth, secondary ossification centers develop and perform 1-4 again
  7. layer of cartilage called epiphyseal cartilage plate (growth plate or physis) persists between epiphysis and the growing end of diaphysis
43
Q

what is the significance of FGFR3

A

it is a negative regulator of chondrocyte proliferation

44
Q

what innervates limbs

A

ventral ramus

45
Q

what do nerve branches go through

A

decision making regions

46
Q

what is significant about decision making regions

A

nerves make up mind on where they want to innervate
brachial plexus- upper limb
lumbosacral plexus- lower limb

47
Q

what is the prevalence of limb defects in live births

A

1:200 live births
not uncommon

48
Q

what are the reduction defects of limb formation

A

meromelia
amelia
phocomelia
adactyly

49
Q

what is meromelia

A

absence of part of a limb
later or partial loss of AER of FGF signaling

50
Q

what is amelia

A

absence of entire limb
early loss of AER or FGF signaling

51
Q

what is phocomelia

A

short, poorly formed limb
partial loss of FGF signaling or Hox disruption

52
Q

what caused phocomelia

A

thalidomide- medication
non genetic cause

53
Q

what weeks are embryos most susceptible to teratogen-induced lumb malformations

A

weeks 4-5

54
Q

what is a consequence of phocomelia

A

angiogenesis inhibition and altered cytokine production

55
Q

what is adactyly

A

absence of digits

56
Q

what is polydactyly

A

duplication defect
extra digits

57
Q

what causes polydactyly

A

upregulation of Shh signaling

58
Q

what is syndactyly

A

dysplasia
fusion of digits

59
Q

what causes syndactyly

A

BMP disruption or Hox13 mutation

60
Q

what causes split foot anomaly and ectrodactyly

A

absence of FGF8 expression
discontinuous AER
dysplasia anomaly

61
Q

what congenital anomaly is amniotic band

A

dysplasia

62
Q

what is amniotic band anomaly

A

adhesion between amnion and affected fetal structure
amnion membrane tears and forms around limbs

63
Q

what is club foot

A

dysplasia
oligohydramnios- insufficient amount of fluid and space for limbs to grow
unrelated to limb rotation!

64
Q

what is achondroplasia

A

short limb dwarfism

65
Q

what inheritance pattern is achondroplasia

A

autosomal dominant

66
Q

what causes achondroplasia

A

activating mutations in FGFR3, which leads to decreased chondrocyte (end of bone) proliferation = short bones

Musculoskeletal/Rheum (3 decks)

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