4. Cell signalling Flashcards
Why is signalling important for multicellular organisms?
Signalling allows cells to coordinate - emergent properties
What are the components of cell signalling process?
- signalling cell
- signalling molecule
- target cell - receptor for signalling molecule
- signal output
How can cell signalling be quantified?
Cell signalling can be quantified by counting signalling genes (signalling proteins) - gives measure of cell’s signalling capacity
Compare unicellular vs multicellular signalling capacity
Unicellular:
- less signalling genes
Multicellular:
- x10 more genes for signalling
- needed for cell communication
What are the possible types of signallling molecules?
- proteins (insulin, growth factors)
- small hydrophobic molecules (animal steroid hormones)
- small hydrophillic molecules (plant auxins)
- gas (ethylene, nitric oxide)
- electrical (nerve impulses)
What is signalling range?
Signalling range - the distance between the signalling cell and target cell
What are the signalling ranges?
- long distance
- intermediate distance
- short distance
Explain long range signalling
Long range signalling:
- endocrine signalling
- transport through bloodstream / plant sap / nervous system
Explain intermediate range signalling
Intermediate range signalling:
- paracrine signalling
- releases signal into local environment - only signalling molecule comes in contact with the target cell (not the signalling cell)
Explain short range signalling
Short range signalling:
- juxtacrine signalling
- signalling and target CELLS come in contact
What are the examples of long range signalling?
- Male and female hormones in sexual dimorphism
- Flowering in plants triggered by daylength
- The nervous system
Explain long range signalling: male and female hormones in sexual dimorphism
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
Explain long range signalling: flowering in plants triggered by daylength
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
What is cell signalling compentence?
Cell signalling competence - ability to respond to a specific signalling molecule
Competent cells - signal responsive cells
Incompetent cells - signal unresponsive cells
Why is cell signalling competence important in long range cell signalling?
In long range signalling - signalling molecule exposed to many different cells - only target cells must respond to the signal - responsive cells - cell signalling competence
Explain long range signalling: in mature / developing nervous system
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
How do nerve cells develop (synapsis development)?
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
Explain axon navigation
Axon navigation:
- axon growth cones navigate growth direction by ‘guidepost’ cell secreted ‘guidepost’ cues
- attractive / repulsive signals from ‘guidepost’ cells
Explain how neurons grow into complex trajectories
Long axon growth path broken down into several steps - each step is guided by ‘guidepost’ cells - secrete guidance cues - attractive / repullsive signals
What range signalling do axon growth cones receive?
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
What type of signalling does the brain use?
Endocrine: hormone signalling - travels in the blood (pituitary, gonads)
Paracrine: nervous system - synapsis (short distance but no contact)
What are the primary sex characteristics?
Reproductive organs (capacity fo the reproductive gland):
- gonads (ovaries / testes)
- gametes (eggs / sperm)
What is sexual dimorphism?
Sexual dimorphism - distinct difference in size / appearance between the sexes in addition to sexual organs (feathers, size, body differences) - secondary sexual characteristics
What are the examples of secondary sexual characteristics?
- size (usually females are larger)
- bodily hair
- body forms
- fur / feather colours
How is sex determined in mammals?
Sex in mammals is determined genetically at fertilisation - XX and XY - sex depends on sex chromosomes
How does the sex develop in a mammalian fertilised egg?
- Sex neutral development (both male and female structures)
- Signalling from Y chromosome (Sry) for male gonad development / no extra signalling for females -> sex specific development
What is Sry?
Sry - a TF encoded by Y chromosome - regulates gene expression for testes differentiation
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 oviduct (Mullerian duct) formation (default development is female)
- Testosterone signals Wolffian duct to develop into vas deferans + secondary male characteristics
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
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
What is the default sex of a mammalian embryo?
Default sex - female - no change unless Sry (male) triggered
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
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
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
What other organism than alligator can use temperature dependent sex determination (TSD) mechanism?
Fish also use TSD - have come and gone through evolution
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
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
What is ‘windowing’ technique in chick eggs?
“Windowing” - surgical manipulatino of the shell to view the embryo on the surface of the yolk sac
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
What are the different body axes?
- anterior-posterior
- dorsal-ventral
- proximal-distal
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)
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)
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)
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
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
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
What is the disorder in Dachshund leg development?
Short leg phenotype due to abnormal expression of FGF4 in developing limbs
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
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
Explain ZPA grafting experiment
Second ZPA grafted into anterior position in embryo - mirror image limb formed (axis of symmetry)
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
What is lateral inhibition?
Lateral inhibition - inihibitory signalling at close range to organise cell structures (ex: neurons, cell spacing)
What is a plant trichomes?
Plant trichomes - ‘hairs’ on plant stems / leaves - trident structure
What are the functions of plant trichomes?
Trichome functions:
-** stinging hairs** to protect from predators
- insect trapping
- seed dispersal
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
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
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
What is the function of hairs on insect surface?
Hairs - sensory bristles on body surface - sense the environment - each bristle connected to sensory neuron
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
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
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
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
Explain autocrine signalling
Autocrine - same cell signalling and targeted - responds to own signals
Signalling lectures summary
What TF regulates trichome formation?
Glabra1 (GL1) regulates trichome formation and development in plants, expressed in trichome precursors
