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MD2002 > Molecular Patterning During Development > Flashcards

Molecular Patterning During Development Flashcards

1
Q

what is intermembranous ossification?

A

+ formation of bone in fibrous connective tissue (which is formed from condensed mesenchyme cells)

+ process occurs during formation of flat bones e.g. mandible, flat bones of skull

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2
Q

in which week of development do the limbs rotate?

A

week 7:

+ upper limbs rotate 90° laterally

+ lower limbs
rotate 90 ° medially

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3
Q

what are HOX genes?

A

during embryonic development they determine body axis and position of limbs along body axis - by acting as morphogen gradients

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4
Q

limb growth is regulated along which 3 axes?

A
  1. proximo-distal
  2. antero-posterior
  3. dorso-ventral
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5
Q

what is proximo distal development controlled by?

A

AER - apical ectodermal ridge

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6
Q

how does AER control proximo-distal development?

A

+ induces underlying tissue to remain as population of undifferentiated rapidly proliferating cells - PROGRESS ZONE

+ as cells move further from AER they begin to differentiate into cartilage and muscle

+ the differentiation results in proximo-distal development

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7
Q

what controls initiation of outgrowth of the forelimb?

A

+ TBX5 gene

+ FGF-10

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8
Q

what does AER secrete that maintains the progress zone and further development of p-d axis?

A

+ FGF4

+ FGF8

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9
Q

FGF4 and FGF8

A
  • secreted by AER

- maintains progress zone and further development of p-d axis

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10
Q

what controls the antero-posterior (cranial-caudal) axis?

A

ZPA - zone of polarizing activity

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11
Q

how does ZPA control a-p axis?

A

+ cluster of cells near the posterior border of limb form ZPA which regulates the AP axis

+ ensures that thumb grows cranial (anterior) side of limb bud

+ ZPA expresses protein, sonic hedgehog (SHH)

+ ZPA moves distally with AER

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12
Q

what protein does ZPA express?

A

SHH - sonic hedgehog

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13
Q

what does adding ZPA to limb bud result in?

A

mirror image duplication of digits

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14
Q

how is dorso-ventral axis controlled?

A

+ BMPs (in ventral ectoderm) induce EN1

+ EN1 represses WNT7 (restricting its expression to dorsal limb ectoderm)

+ WNT7 induces LMX1 (which specifies the cells to be dorsal)

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15
Q

what is expression HOX gene dependent of?

A

SHH, FGFs and WNT7a

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16
Q

what is amelia?

A

complete absence of limbs

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17
Q

what is meromelia?

A

partial absence of limbs

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18
Q

what is phocomelia?

A

absence of long bones

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19
Q

what is micromelia?

A

segments that are abnormally short

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20
Q

what is the term for complete absence of limbs?

A

amelia

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21
Q

what is the term for partial absence of limbs

A

meromelia

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22
Q

what is the term for absence of long bones?

A

phocomelia

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23
Q

what is the term for segments that are abnormally short?

A

micromelia

24
Q

what conditions were caused by thalidomide?

A

+ amelia

+ phocomelia

25
Q

what causes Holt Oram Syndrome?

A

TBX5 mutation

26
Q

what is the result of Holt Oram Syndrome?

A

+ upper limb deformities

+ heart defects

27
Q

what is the result of brachydactyly?

A

short digits

28
Q

what is the result of syndactyly?

A

fused digits - failure of apoptosis

29
Q

what is the result of polydactyly?

A

extra digits

30
Q

what is the result of cleft foot?

A

lobster claw deformity

31
Q

which defect results in short digits?

A

brachydactyly

32
Q

which defect results in fused digits due to failure of apoptosis?

A

syndactyly

33
Q

which defect results in extra digits?

A

polydactyly

34
Q

which defects results in a lobster claw deformity?

A

cleft foot

35
Q

when and where do upper limb buds appear?

A
  • approx. day 24

- between somites C5-T1

36
Q

when and where do lower limb buds appear?

A
  • approx. on day 28

- between somites L2-S2

37
Q

when are all major components of limbs present?

A

by week 8

38
Q

what does the limb bud consist of?

A
  • core of mesenchyme derived from parietal layer of lateral plate mesoderm
  • ectoderm which forms the outer covering of the limb (epidermis)
  • ectoderm is thickened at the ‘apex’ of developing limbs to form the Apical Ectodermal Ridge (AER)
39
Q

what does HOX-8 control?

A

position of the limb on the long axis of the body

40
Q

what does TBX5 and FGF-10 control?

A

initiation of outgrowth of fore limb

41
Q

steps in AER controlled proximo-distal development

A
  1. HOX-8 controls the position of the limb on long axis of body
  2. initiation of outgrowth of fore limbs is controlled by TBX5 and FGF-10
  3. AER secretes FGF4 and FGF8to maintain the progress zone and the further development of the proximo-distal axis
  4. as growth progresses, mesenchymal cells are left behind the advancing ridge (and its influence) and so they begin to differentiate
42
Q

BMPs

A
  • in ventral ectoderm

- induce EN1

43
Q

EN1

A
  • represses WNT7, restricting its expression to the dorsal limb ectoderm
  • induced by BMPs
44
Q

WNT7

A
  • induces LMX1

- repressed by EN1

45
Q

LMX1

A
  • induced by WNT7

- specifies the cells to be dorsal

46
Q

what do variations in the combinations of HOX genes ensure?

A
  • upper and lower limbs are different TBX5 (upper), TBX4 (lower)
  • patterns for the proximal (arm), middle (radius and ulna) and distal (hand) are defined
47
Q

incidence of limb defects

A
  • limb malformations occur in approx 3.8-1000 live births
  • UL abnormalities more common that LL
  • limbs defects often associated with other abnormalities affecting CVS, GU system and craniofacial structures
  • cause may be hereditary but also by environmental (teratogens)
  • affects the progress zone with failures of cell division (weeks 4&5)
48
Q

what abnormalities of the limbs were seen as a result of thalidomide?

A
  • phocomelia / amelia
  • flipper-like arms or legs
  • associated with intestinal atresia and cardiac abnormalities
49
Q

TBX5

A

mutation leads to defects in limb development (Holt Oram Syndrome)

50
Q

what are the 2 stages of commitment?

A
  1. specification (reversible)
    - capable of differentiating autonomously if placed in isolation BUT can be respecified if exposed to certain chemicals/signals
  2. determination (irreversible)
    - cell will differentiate autonomously even when exposed to other factors or placed in a different part of the embryo
51
Q

how does a naive cell become specified?

A
  • intrinsic signal: cell autonomous signal tells cell ‘who it is’
  • extrinsic signal: a chemical or molecule int he environment gives the cell spatial information, tells the cell ‘ where it is’
52
Q

cell fate

A
  • what it will become in the course of normal development

- when a cell “choose” a particular fate, it is said to be determined

53
Q

progress of a cell during development

A
  1. naive
  2. specified
  3. determined
  4. differentiated
54
Q

competence of a cell

A
  • ability to respond to chemical stimuli

- can lose competence by changes in surface receptor or intracellular molecules

55
Q

bivalent chromatin

A
  • segments of DNA, bound to histone proteins, that have both repressing and activating epigenetic regulators in the same region
  • work to enhance or silence the expression of genes
  • both types of regulators are interacting with the same domain at the same time
56
Q

developmental regulatory genes (transcription factors)

A

e.g. HOX, SOX, T-box

MD2002 (85 decks)

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