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Medicine 2.1 > Cell Differentiation and Limb Development > Flashcards

Cell Differentiation and Limb Development Flashcards

1
Q

What is cell differentiation?

A
  • Process of cell changing from one cell type to another.

- Mostly, a less specialised cell to a more specialised cell

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2
Q

What controls cell differentiation?

A
  • Many factors:

- Transcription factors

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3
Q

What are transcription factors?

A

-Regulators that can act at different stages and in deifferent combination through the path of cell development and differentiation.

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4
Q

How can cell differentiation effect a cell?

A
  • Size
  • Shape
  • Membrane potential
  • Metabolic activity
  • Responsiveness to signals
  • Different cells have different characteristics despite having the same genome
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5
Q

When does limb development occur?

A

From week 4-8

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6
Q

What do limbs develop from?

A

-Small buds of undifferentiated mesoderm cells which are covered by ectoderm

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7
Q

What happens/is visible by end of week 4?

A
  • Limb buds become visible for first time
  • Upper limb buds appear first as ridges from ventrolateral body wall
  • Lower limb as small bulges
  • Lower limb slightly behind, but catches up by end of developmental period
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8
Q

What is the 1st sign of limb musculature?

A

-Appearance of condensation of mesenchyme near limb buds

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9
Q

What is mesenchyme derived from?

A

-Dorsolateral or ventrolateral mesoderm cells of the somites

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10
Q

Are their nerves in the early limb bud?

A

NO

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11
Q

What do limb buds consist of?

A
  • Mesenchymal core (from somatic layer of lateral plate mesoderm)
  • Covered by layer of cuboidal ectoderm
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12
Q

What does the ectoderm do at the distal end of the limb bud and why is this area different?

A
  • Forms apical ectodermal ridge

- This has inductive relationship with mesoderm and remaind undifferentiated

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13
Q

What is the importance of the AER?

A
  • As limb grows the cells furthest from AER begin to differentiate into cartilage and muscle.
  • Without AER limbs fail to develop as it is a key signalling centre
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14
Q

What initiates limb outgrowth?

A

FGF 10

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15
Q

What does the position of AER correspond to?

A

-Border between dorsal and ventral ectoderm

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16
Q

What is a difference in how UL and LL development is controlled?

A

Different factors designated to UL and LL

  • TBX-5 in UL
  • TBX-4 in LL
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17
Q

Describe relationship between mesoderm and ectoderm interaction and its importance?

A
  • Essential
  • AER-promote mitosis and prevents differentiation
  • Although AER is acting on mesoderm, its own existence is controlled by the mesoderm
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18
Q

What happens at week 6 of limb development?

A
  • Terminal portions of buds become flattened: -hand plates and foot plates
  • Separated from proximal segments by constriction
  • 2nd constriction further divides proximal portion into 2 segments
  • Development proceeds proximodistally into 3 components
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19
Q

What 3 portions are limbs split to during week 6?

A
  • Stylopod: humerus and femur
  • Zeugopod: radius/ulna and tibia/fibula
  • Autopod: carpals,MCP,digits,tarsals,metatarsals
20
Q

What is FGF 10 and where is it first seen?

A

A paracrine signalling molecule 1st seen in limb buds

21
Q

What is FGF family known for?

A

-Mitogenic activity (inducing cell to begin division via triggering a signal transduction pathway)

22
Q

What signalling molecules help specify the dorsoventral axis around the AER?

A
  • Radical fringe: expressed by dorsal ectoderm

- Engrailed-1: expressed by ventral ectoderm (TF)

23
Q

What does AER express for maintenace of undifferentiated zone?

A

Once ridge is established it expresses FGF 4 and 8

24
Q

What regulates positioning of limbs along craniocaudal axis and how is this expressed and what does misexpresion lead to?

A
  • HOX genes
  • Expressed in overlapping patterns
  • Mis expression alters limb position
25
Q

What does cell death in the AER do during limb development?

A
  • Separates ridges into 5 parts: 5 digits gow out under inlfuence of 5 ridge parts
  • Mesenchyme condense to form cartilaginous digits
  • By day 56, digit seperation is complete
26
Q

What regulates limb outgrowth?

A

-FGF 10

27
Q

What do FGF 4, 8 and Retinoic acid do?

A
  • FGF 4 and 8 at distal end keep cells undifferentiated

- Retinoiic acid at proximal end starts differentiation into proximal components

28
Q

What is polydactyly and what causes it and how is it inherited?

A
  • Extra digits
  • Defect in mesoderm caused by mutations in HOX genes, Sonic hedgehog or Wnt
  • Inherited in humans as genetic recessive trait
29
Q

When and how does limb rotation occur?

A
  • Week 7

- Upper and lower limbs rotate in opposite directions

30
Q

How does the UL rotate and why?

A
  • 90 degrees laterally

- Allows extensor muscles to lie on lat and post side, makes thumb lateral and elbow pointing back

31
Q

How does LL rotate and why?

A
  • 90 degrees medially

- Allows extensor muscles to lie ant., big toe to be medial and knees to face forward

32
Q

What are some things that may go wrong during limb development?

A
  • Conditions affecting UL more common
  • Faliure of formation: amelia, meromelia
  • Failure of differentiation: sirenomelia, synostoses
  • Duplication
  • Overgrowth: hemihypertrophy
  • Undergrowth: micromelia
  • Contriction band syndrom: would need amputatio nat certain levels
  • Generalised abnormalities: marfans, achondroplasia
33
Q

Describe start of limb bone development?

A
  • As external shape is being established, mesenchyme in the buds becomes condensed
  • Cells differentiate into chondrocytes
  • At week 6 hyaline cartilage models can be seen
  • Areas where chondrogenesis is arrested makes joints
34
Q

What drives mesenchyme cell differentiation to chondrocytes?

A

BMP expression

35
Q

Where do centres of ossification form in long bone?

A
  • Diaphysis

- Epiphysis

36
Q

By when are primary centres present in all bone?

A

-week 12

Cartilage growth plate remains

37
Q

At birth what happens?

A
  • Epiphysis still cartilaginous

- Secondary centres disappear

38
Q

What happens at puberty?

A

-Growth plates close

39
Q

During the bone growth period what does remodelling and why?

A

-Osteoclasts to retain overall shape and proportion

40
Q

What does achondroplasia effect?

A
  • Enchondral ossification via cartilage, particularly long bones of arms and legs
  • Autosomal dominant mostly, due to specific mutation
41
Q

How would achondroplasia be diagnosed?

A
  • Ultrasound

- 20 weeks scan when long bones can be measured

42
Q

What can happen if both parents have the gene?

A

-1 in 4 chance of lethality

43
Q

What causes achondroplasia?

A

Mutation in FGF 3 which normally downregulates cartilage and bone growth and inhibits cell proliferation and differentiation.
-Mutation causes permamnent expression so sreduced chondtrocyte activity

44
Q

Is there a cure for achondroplasia and what problems may arise?

A
  • NO
  • But should be able to live healthy independant life
  • Some may get breathing issues, curvature of spine issues or walking issues
  • Limb strengthening surgery may be used but is painful and no guarantee it will work
45
Q

Are recent therapies for achondroplasia looking promising?

A
  • yes eg. vosoritide

- Advances in tech for FGF 3 mutation correction( CRISPR/Cas9) but still not too close (not in clinical trials)

Medicine 2.1 (29 decks)

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