4. Cell signalling Flashcards

(79 cards)

1
Q

Why is signalling important for multicellular organisms?

A

Signalling allows cells to coordinate - emergent properties

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2
Q

What are the components of cell signalling process?

A
  • signalling cell
  • signalling molecule
  • target cell - receptor for signalling molecule
  • signal output
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3
Q

How can cell signalling be quantified?

A

Cell signalling can be quantified by counting signalling genes (signalling proteins) - gives measure of cell’s signalling capacity

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4
Q

Compare unicellular vs multicellular signalling capacity

A

Unicellular:
- less signalling genes

Multicellular:
- x10 more genes for signalling
- needed for cell communication

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5
Q

What are the possible types of signallling molecules?

A
  • proteins (insulin, growth factors)
  • small hydrophobic molecules (animal steroid hormones)
  • small hydrophillic molecules (plant auxins)
  • gas (ethylene, nitric oxide)
  • electrical (nerve impulses)
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6
Q

What is signalling range?

A

Signalling range - the distance between the signalling cell and target cell

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7
Q

What are the signalling ranges?

A
  • long distance
  • intermediate distance
  • short distance
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8
Q

Explain long range signalling

A

Long range signalling:
- endocrine signalling
- transport through bloodstream / plant sap / nervous system

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9
Q

Explain intermediate range signalling

A

Intermediate range signalling:
- paracrine signalling
- releases signal into local environment - only signalling molecule comes in contact with the target cell (not the signalling cell)

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10
Q

Explain short range signalling

A

Short range signalling:
- juxtacrine signalling
- signalling and target CELLS come in contact

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11
Q

What are the examples of long range signalling?

A
  • Male and female hormones in sexual dimorphism
  • Flowering in plants triggered by daylength
  • The nervous system
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12
Q

Explain long range signalling: male and female hormones in sexual dimorphism

A

Male and female hormones in sexual dimorphism:
- gonads secrete hormone cocktails - signalling molecules
- sensed by cells in the body
- target cells develop ‘male’ / ‘female’ appearance

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13
Q

Explain long range signalling: flowering in plants triggered by daylength

A

Flowering in plants triggered by daylength:
- sunlight - signal
- sunlight sensor (receptor) - CO protein in leaf - CO accumulates when days are long
- high CO levels promote FT protein synthesis
- high FT levels - moves through sap into leaf shoot
- FT stimulates flowers to form at the shoot

Allows same species to synchronise flowering; important for cross pollination - flowers need other flowers for pollination

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14
Q

What is cell signalling compentence?

A

Cell signalling competence - ability to respond to a specific signalling molecule

Competent cells - signal responsive cells
Incompetent cells - signal unresponsive cells

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15
Q

Why is cell signalling competence important in long range cell signalling?

A

In long range signalling - signalling molecule exposed to many different cells - only target cells must respond to the signal - responsive cells - cell signalling competence

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16
Q

Explain long range signalling: in mature / developing nervous system

A

Mature nervous system:
- long range signalling (neurons - elaborate shapes + connect to form functional circuits - nerve signal travels long distance)
- signalling within the brain + from the brain to periphery
- Signal travels long distance but signalling is paracrine: pre-synaptic (signalling) and post-synaptic (target cell) contact each other at synapse - neurotransmitter secreted into synaptic cleft (close but no contact) – at the end of motor neurons - signal transmitted into muscle cells

Developing nervous system:
- short range signalling in nervous system developement

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17
Q

How do nerve cells develop (synapsis development)?

A

Nerve cells must connect to each other to form synapsis:
- nerve cells grow out axons to the target nerve cell:
- axon navigation: part of neuron - growth cone navigates
- the growth direction sensed by growth cone from ‘guidepost’ cells - secrete guidepost cues in the tissue
- complex trajectories form by breaking long journies into several steps

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18
Q

Explain axon navigation

A

Axon navigation:
- axon growth cones navigate growth direction by ‘guidepost’ cell secreted ‘guidepost’ cues
- attractive / repulsive signals from ‘guidepost’ cells

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19
Q

Explain how neurons grow into complex trajectories

A

Long axon growth path broken down into several steps - each step is guided by ‘guidepost’ cells - secrete guidance cues - attractive / repullsive signals

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20
Q

What range signalling do axon growth cones receive?

A

Paracrine (intermediate):
- growth cone reacts to signals in the local environment (no contact between cells)

Juxtacrine (in contact) signalling:
- growth cone reacts to signals in contact with the signaling cell

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21
Q

What type of signalling does the brain use?

A

Endocrine: hormone signalling - travels in the blood (pituitary, gonads)

Paracrine: nervous system - synapsis (short distance but no contact)

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22
Q

What are the primary sex characteristics?

A

Reproductive organs (capacity fo the reproductive gland):
- gonads (ovaries / testes)
- gametes (eggs / sperm)

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23
Q

What is sexual dimorphism?

A

Sexual dimorphism - distinct difference in size / appearance between the sexes in addition to sexual organs (feathers, size, body differences) - secondary sexual characteristics

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24
Q

What are the examples of secondary sexual characteristics?

A
  • size (usually females are larger)
  • bodily hair
  • body forms
  • fur / feather colours
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25
How is sex determined in mammals?
Sex in mammals is determined **genetically** at fertilisation - XX and XY - sex depends on **sex** **chromosomes**
26
How does the sex develop in a mammalian fertilised egg?
1. **Sex neutral development** (both male and female structures) 2. **Signalling from Y** chromosome (Sry) for male gonad development / **no extra signalling** for females -> **sex specific development**
27
What is Sry?
**Sry** - a **TF** encoded by Y chromosome - regulates gene expression for **testes differentiation**
28
Explain male sex determination in XY
- In sex neutral development **both male and female structures** present (indifferent state) - **Sry expressed** - **Mullerian inhibiting** substance secreted - **inhibits oviduc**t (Mullerian duct) formation (default development is female) - **Testosterone** signals **Wolffian duct** to develop into **vas deferans** + **secondary male characteristics**
29
Explain long range testosterone signalling
Testosterone (hydrophobic, steroid hormone) secreted by gonads - acts on **distant target cells** (long range signalling) via **blood** - binds to cell receptors - regulates **gene expression** in targeted cells
30
Explain female sex determination in XX
- In sex neutral development **both male and female structures** present (indifferent state) - **Sry absent** - gonads develop into **ovaries** - **Wolffian duct disappears** - oviduct develops - **No testosterone** made - **no Mullerian inhibiting** substance - no male structures develop - ovaries secrete **female hormones**
31
What is the default sex of a mammalian embryo?
Default sex - **female** - no change unless Sry (male) triggered
32
What kind of signalling is used when gonads secrete hormones for sexual dimorphism?
**Long range** signalling - **endocrine**: hormones secreted by gonads and **transported in blood** around the body - **only target cells contain receptors** for sexual hormones - induced changes - sexual dimorphism
33
What is the disorder making XY human unresponsive to sex hormones?
CAIS (**complete androgen insensitivity syndrome**): some **XY lack receptors for androgens** and have **internal testes** - **develop as females** at puberty => response to **androgen signals** from testes is **essential for male** characteristic development (because default is female)
34
What are androgens?
Androgen - a male sex hormone
35
How is genetic sex determination in birds different to humans?
Also use unequally sized chromosomes - W and Z: **ZZ male** (homozygous), **ZW female** (heterozygous)
36
Is sex development in bird embryo same as in human?
Yes, initially embryos are **sexually indifferent** (sex nuetral development) -> **sex chromosomes signal** -> sex specific development
37
Can birds have both male and female features at the same time?
Yes but **disorder**: - **gynandromorphs** - have both male and female dimorphisms - **mixture of ZZ and ZW cells** - although all cells are exposed to same hormones - have **intrinsic sex identity** (hormone interpretation is questioned) - **CELL AUTONOMOUS** sex determination => **primary component driving sex differentiation** in birds is **not long range hormone signalling**
38
How can a mix of genetically distinct cells arise in an organism?
- **Mosaic**: due to **genetic change in cell lineage** derived from single zygote - **Chimera**: due to **fusion of genetically distinct embryos** => the result/effect is the same mixture fo cells
39
What are the three main types of sex determination methods?
- **genetic** determination (humans) - **cell autonomous** sex determination (birds) - **temperature dependent** determination (alligators)
40
Explain how sex determination occurs in alligators?
Sex determination - temperature dependent (not genetically): - lay eggs outside of body - incubate - incubation temperature determines sex phenotype - warm >34 - male; cold <30 - female - **temperature acts as a signal**
41
What other organism than alligator can use temperature dependent sex determination (TSD) mechanism?
Fish also use TSD - have come and gone through evolution
42
What type of signalling is used by morphogens/development signalling molecules in organism development?
**Paracrine** (intermediate range) signalling (<1mm range: 1-100 cell diameters)
43
Suggest an example to study paracrine signalling during development? Why useful?
Pentadactyl limb development - 5 digit structure conserved between tetrapods - can compare between species + easier experimentally (no humans used) - **paracrine signalling** from **growth plates** to **limb ends** - in the local environment
44
How is pentadactyl limb development similar/ different between species?
**Early development - conserved **between species (very similar structures) - as development progresses - **developing structures diverge** into different shapes and sizes
45
What is 'windowing' technique in chick eggs?
"Windowing" - surgical manipulatino of the shell to view the embryo on the surface of the yolk sac
46
Explain limb formation in the chick embryo
- Limb formation starts 3 days after fertilisation - **Anterior limb bud** (wing bud) and **posterior limb bud** (leg bud) - signalling over <1mm can aid to develop the whole limb - **morphogen gradient** - signalling molecule presence determines the developing limb structure at a particular place
47
What are the different body axes?
- anterior-posterior - dorsal-ventral - proximal-distal
48
What are the limb axes?
- **Proximo-distal axis**: proximal wrist (close to the body) - distal fingertips (far from the body) - **Anterio-posterior axis**: anterior thumb (to the front) - posterior little finger (to the back)
49
How do chick wing and human hand digits vary?
**Human hand**: pentadactyl developed into **5 digits** **Chick wing**: pentadactyl limb **lost digits 1 and 5** in evolution (maybe for lighter wings)
50
How is cell fate decided along the three body axes?
Paracrine signalling: - patterning of the embryo - growth (cell division) within petterning - cell signalling
51
Explain limb development in proximo-distal axis
Proximo-distal axis (near-far the body): - **apical ectoderm ridge (AER)** at the **tip of limb bud** - important for proximo-distal development - AER is important over the whole limb development period - AER contains **FGF4** (fibroblast growth factor) signalling molecule used **for proximo-distal limb development** - proximo-distal limb development **not autonomous** - responds to the **external signal of FGF4** (tested in FGF4 injection in wrong cells)
52
Explain AER removal experiment
- AER (apical ectoderm ridge) **surgically removed** from wing bud at different development stages - development allowed to proceed => **the later the AER was removed, the more distal structure formed**
53
Explain how was the molecular AER mechanism discovered?
- AER (apical ectoderm ridge) **surgically removed** - signalling molecules (FGF4) introduced into tissues by **FGF4 soaked beads** -> **proximo-distal limb still developed** => **AER** needed in development because **releases signalling molecules**
54
How was it determined that FGF4 is sufficient for proximo-distal limb development?
- **FGF4 soaked beads** were applied to a **wrong location** on chick embryo prodcued **extra limb bud** (ectopic limb bud) - induced leg
55
What is an ectopic limb bud?
**An extra limb bud** which development was **induced artificially**
56
What is the disorder in Dachshund leg development?
**Short leg phenotype** due to **abnormal expression of FGF4** in developing limbs
57
Explain limb development in anterior-posterior axis
Anterior-posterior axis: - driven by **morphogen gradients** - **different gradient thresholds** of same morphogen **for different structures** (French flag model) - source of morphogen is the posterior end: high threshold for posterior structures, low threshold for anterior structures - **zone of polarising activity (ZPA)** - ZPA secretes **sonic hedgehog (Shh)** morphogen **for anterior-posterior limb development** in different gradients - cells are **dependent on external signal to develop** (not autonomous) and all cells can respond to Shh (grafting experiment) - **Shh is master regulator of organogenesis**
58
What's the french-flag model in development
**Different gradients** of the **same morphogen** drive development of **different structures** - secreted from one place - as morphogen diffuses - different gradients created - different thresholds needed for different structures to develop
59
Explain ZPA grafting experiment
**Second ZPA grafted into** anterior position in embryo - **mirror image limb formed** (axis of symmetry)
60
How was it investigated if Shh is sufficient for anterior-posterior limb development?
**Shh** expressing cells were **grafted into anterior side** of limb bud - full **mirror image limb** structures developed => **Shh is sufficient to drive anterior-posterior** limb axis development
61
Define what is a morphogen
**Morphogen** - substance active in **pattern formation** whose **concentration varies** in space and to which **cells respond differently at different thresholds** (ex: Shh but NOT FGF4 - on/off mechanism)
62
What is an organiser?
**Organiser** - a **signalling center** that directs development of the whole / part of an embryo (ex: ZPA, AER)
63
What is lateral inhibition?
**Lateral inhibition** - **inihibitory** signalling at **close range** to organise cell structures (ex: neurons, cell spacing)
64
What is a plant trichomes?
Plant trichomes - 'hairs' on plant stems / leaves - trident structure
65
What are the functions of plant trichomes?
Trichome functions: -** stinging hairs** to protect from predators - **insect trapping** - **seed dispersal**
66
Explain how plant trichomes differentiate
- Differentiate from **epidermal precursor cells** - all the same - One cells becomes **selected for trichome** - **trichome precursor** -> differentiation into trichome - **Lateral inhibition** - trichomes spaced out
67
What properties must be regulated for plant trichome to function properly?
- Trichome spacing (pattern formation) - Trichome anatomy (differentiation of individual trichomes)
68
Explain trichome spacing
Trichomes at different densities in different plants - spacing needed - **mechanism** for spacing - **must allow variable spacing**: - each epidermal cell has chance for trichome - **non-random pattern** - trichomes never touch - depending on **signal from surrounding cells** (non-cell autonomous) - **lateral inhibition** - inhibits neighbours not to become trichome - **tryptochon** gene - higher/lower **trichome densities** achieved by **signal gradient**
69
Explain tryptochon mutation in plant trichome development
Tryptochon mutants - **break no touching rule** in trichome spacing - disruption of signalling => **gene tryptochon ensures trichome spacing** by lateral inhibition
70
What are the biological examples of cell spacing based on juxtacrine signalling?
- Plant **trichomes** (lateral inhibition of adjacent cells) - **Hair spacing on insect surface** (lateral inhibition of adjacent cells) - **Tree spacing** in forests (*resource depletion* - irregular patern)
71
What is the function of hairs on insect surface?
Hairs - **sensory bristles** on body surface - sense the environment - each bristle connected to sensory neuron
72
How are insect sensory bristles arranged at a regular pattern?
**Juxtacrine** (ell-cell contact) **lateral inhibition** - where bristle formed also sensory neuron - **bristle neurons never formed close** - **Notch inhibitory signalling pathway**
73
Explain laser ablation experiment on insect bristle spacing
Laser ablation experiment: - Laser used to **kill bristle precursor cells** only on the right embryo side - left was control - Single bristle formed nearby the destroyed - **all cells have the potential to become bristle cells** - when one becomes - others inhibited - **lateral inhibition**
74
How regeneration of gut villi is maintained?
Gut villi in **eroding env**. - **cells shed** from the tip - need to be replaced - **stem cell differentiation** - all cells move up - restore lost cells Repulsive signalling between EphB and ephrinB restricts stem cell movement out of the crypt
75
Explain how cell-cell contact repulsion helps to maintain gut villi development? How stem cells don't escape the crypt?
Cell-cell contact helps in inwardly buckled crypt structure development - uses EphB / EphrinB repulsion: - **mutual repulsion** by signalling between **EphB** (**proliferating stem cells**) and **ephrinB** (**flanking cells**) - transmembrane proteins - cells separate - minimise area where cells with EphB and ephrinB come in contact => **stem cells proliferate** but **can't escape the crypt** because it would involve mixing with flanking cells
76
What are the mechanisms where Eph/Ephrin contact dependent repulsion is used?
- in **gut villi** constant renewal - in axon **growth cone** navigation
77
Explain autocrine signalling
Autocrine - same cell signalling and targeted - responds to own signals
78
Signalling lectures summary
79
What TF regulates trichome formation?
Glabra1 (GL1) regulates trichome formation and development in plants, expressed in trichome precursors