Medicine 2.1 > Cell Differentiation and Limb Development > Flashcards

Cell Differentiation and Limb Development Flashcards

(45 cards)

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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?

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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?

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A

A paracrine signalling molecule 1st seen in limb buds

21
Q

What is FGF family known for?

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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?

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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?

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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?

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A
  • HOX genes
  • Expressed in overlapping patterns
  • Mis expression alters limb position
25
What does cell death in the AER do during limb development?
- 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
What regulates limb outgrowth?
-FGF 10
27
What do FGF 4, 8 and Retinoic acid do?
- FGF 4 and 8 at distal end keep cells undifferentiated | - Retinoiic acid at proximal end starts differentiation into proximal components
28
What is polydactyly and what causes it and how is it inherited?
- Extra digits - Defect in mesoderm caused by mutations in HOX genes, Sonic hedgehog or Wnt - Inherited in humans as genetic recessive trait
29
When and how does limb rotation occur?
- Week 7 | - Upper and lower limbs rotate in opposite directions
30
How does the UL rotate and why?
- 90 degrees laterally | - Allows extensor muscles to lie on lat and post side, makes thumb lateral and elbow pointing back
31
How does LL rotate and why?
- 90 degrees medially | - Allows extensor muscles to lie ant., big toe to be medial and knees to face forward
32
What are some things that may go wrong during limb development?
- 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
Describe start of limb bone development?
- 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
What drives mesenchyme cell differentiation to chondrocytes?
BMP expression
35
Where do centres of ossification form in long bone?
- Diaphysis | - Epiphysis
36
By when are primary centres present in all bone?
-week 12 | Cartilage growth plate remains
37
At birth what happens?
- Epiphysis still cartilaginous | - Secondary centres disappear
38
What happens at puberty?
-Growth plates close
39
During the bone growth period what does remodelling and why?
-Osteoclasts to retain overall shape and proportion
40
What does achondroplasia effect?
- Enchondral ossification via cartilage, particularly long bones of arms and legs - Autosomal dominant mostly, due to specific mutation
41
How would achondroplasia be diagnosed?
- Ultrasound | - 20 weeks scan when long bones can be measured
42
What can happen if both parents have the gene?
-1 in 4 chance of lethality
43
What causes achondroplasia?
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
Is there a cure for achondroplasia and what problems may arise?
- 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
Are recent therapies for achondroplasia looking promising?
- yes eg. vosoritide | - Advances in tech for FGF 3 mutation correction( CRISPR/Cas9) but still not too close (not in clinical trials)
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