3. VL Flashcards

C. elegans I C. elegans: cell lineage, signal transduc2on and programmed cell death

1
Q

Caenorhabdis elegans is a …. and was first described in …. by….

A

roundworm; 1900; Emile Maupas

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2
Q

Advantages of the model organism

A
  • Benign for humans.
  • Optical transparency.
  • Organogenesis/physiology: „in miniature“
  • Many protocols established: mutagenesis, transgenesis, molecular biology,..
  • Easy to breed and maintain.
  • Small size (approx. 1 mm long and 40 μm wide).
  • Rapid life cycle (3-3.5 days).
  • Large brood size
  • Can be frozen and stored at -80°C for more than 10 years.
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3
Q

Facts about C. elegans

A
Six chromosomes (linkage groups): 5 autosomes I-V, 1 sex chromosome X - containing 20.444 protein-coding genes Two genders: Hermaphrodites, Males
 Hermaphrodites: Selffertlization, Egg and sperm from same animal -> Offspring clones - no variation
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4
Q

What do you know about the genetics in C. elegans?

A
  • First multicellular eukaryoic organism with a fully sequenced genome (1998).
  • 38% of C. elegans protein coding genes have predicted orthologs in the human genome.
  • Invariant development.
  • Constant cell numbers
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5
Q

Limitations of that model organism

A
  • Small size.
  • Dissection almost impossible
  • No cell culture lines exist.
  • Not all metazoan genes are found in C. elegans genome.
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6
Q

What tissues owns an adult hermaphrodite C. elegans?

A

Pharynx, Uterus, proximal gonades, distal gonades, intestine, anus

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7
Q

How is the somatic muscle built up?

A

type: striated (gestreift)
95 diamond shaped body-wall muscle cells
4 quadrants run along side the length of the animal lead to the sinusoidal movement of the animals

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8
Q

C. elegans: model for… (diseases)

A

Duchenne’s Muscular Dystrophy (DMD) and cardiomyopathies.

Mutation in dystrophin caused DMD

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9
Q

C. elegans: the intestine - what do you know? How is it built up?

A
  • 20 large epithelial cells form a long tube around the lumen.
  • only fixed to pharynx and rectum.
  • only one associated muscle at the posterior end.
  • not directly innervated.
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10
Q

What functions have the intestine of C. elegans?

A
  1. digestion of food
  2. absorption of processed nutrients
  3. synthesis and storage of macromolecules
  4. initiation of an innate immune response to pathogens
  5. nurturing of germ cells by producing yolk
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11
Q

the intestine of C. elegans is a model for…?

A
  1. organogenesis
  2. morphogenesis
  3. cell fate (pharynx)
  4. infection and response to infection (intestine)
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12
Q

What is the C. elegans excretory system a model for?

A

for tube formation

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13
Q

What do you know about the C. elegans - nervous system?

A
  • Hermaphrodites 302 neurons / males 382 neurons.
  • Mostly simple structure with one or two neurites exiting from the cell body.
  • Passive nerve conduction: No sodium-dependent action potentials. High membrane resistance.
  • Various neurotransmisers and receptors involved.
  • Multi-functional neurons (polymodality), probably because of the low number.
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14
Q

C. elegans - nervous system is an important model for…

A

…Neurobiological questions
< 7000 chemical synapses & gap junctions connections
• connectome (Gesamtheit der Verbindungen des Nervensystems) known
–> Cell Lineage studies!

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15
Q

For what is the reproduction system of. C. elegans a model?

A
  1. morphogenesis
  2. sex-specific anatomy
  3. programmed cell death
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16
Q

How are male mating and self mating differ from each other?

A
  • Selfing: approx. 300 progenies

* Mating: approx. 1000 progenies (male sperms preferred)

17
Q

Where can you find information about C. elegans in the web?

A

Wormbook (anatomy), wormbase (genetics), wormatlas (anatomy), Caenorhabdi2s Genetics Center (wildtype and mutants)

18
Q

Topic: Mutagenesis: what mutations are happening spontaneously and what are they caused by?

A

point mutation, gene duplication, deletions

caused by: repair errors, endogenous oxidative damage, exogenous environmental insult

19
Q

What are the 3 mutagenesis strategies?

A
  1. Genome-wide mutagenesis (forwardgenetics): The whole genome is mutagenized to identify genes that are involved in a specific process, e.g. developmental or physiological.
  2. Target-selected mutagenesis (reverse genetics): The whole genome is mutagenized, but only a specific target gene is screed for mutations.
  3. Gene-targeted mutagenesis (reverse genetics): A target gene is specifically mutagenized.
20
Q

C. elegans in space - what does scientists found out working on the International C. elegans first experiment - ICE-FIRST in 2004?

A

experiment took place in space (Strahlendosis 150 fach höher als auf Erdoberfläche) –> after 11 days no real mutations noticed –> DNA repair mechanism worked efficiently and that spontaneous alterations (Änderungen) to the genome may result from cell- intrinsic errors

21
Q

What mutants of the C. elegans do you know?

A

uncoordinated - Unc

roler - Rol

22
Q

How does “suppressor screen” works?

A

Chemical induced mutation –> Screening for potential signaling partners

23
Q

one of the biggest discoveries in C. elegans was the study from John Sulston and Sydney Brenners about the Cell linage. What exactly did they want to find out and how did they do this?

A

wanted to understand the nervous system –> useful to gather knowledge about the development of the nervous system of C. elegans. Sulston started with ventral nerve cord and used differential interference contrast (DIC) optics (looked at the animals alive)
took Sequential photographs of an L1 hermaphrodite
result: found our about: complete post-embryonic cell lineage (Sulston) and later about the embryonic cell lineage

24
Q

For which founding Horwitz, Brenner and Sulston got the nobel price for?

A
  • Invariant cell divisions generate a fixed no. of progeny cells of rigidly determined fates.
  • Three main events occur during post- embryonic development: Cell division, Cell migration, Cell death
25
Q

What can we learn from Vulva Development in C. elegans?

A

Signal Transduction
• Vulva has defined set of different cell types: 1 0, 2 0 and 3 0
• Interesting communication between different cell types.
you need and anchor cell for make differentiation start. this changes the neighbors of a 1 0 cell into a 2 0 cell, and the next one into a 3 0 cell
the ablation of the gonade and / or the anchor cell does not change the cell fate (multi-vulva mutants)

26
Q

How do Signaling pathways are taking place?

A

Reception (Hormon or sinal molecule binds to receptos in plasma membrane), Transduction: relay molecules make the signal go on in , Response: activation of cellular responses

27
Q

What types of programmed cell death had been described?

A
  1. Apoptosis (in C. elegans)
  2. Autophagy
  3. Necroptosis…
28
Q

Apoprosis happens in C. elegans. What 2 types do you know?

A
  1. Developmental cell death (131 cells die, 105 cells of the nervous system)
  2. Germ cell death (> 50 % of all germ cells die)
29
Q

meaning of apoptosis in C. elegans?

A

C. . elegans does not need apoptosis for proper development. Genes involved in apoptosis might be essential for innate immune response.
Mutant that effect the apoptosis are viable and fertile, but:
- grow slower
- smaller brood size
- fail to eliminate damaged germ cells following genotoxic stress
- hyper-suscepzible to infections.

30
Q

genes that takes part of apoptosis?

A

ced-3, ced-1, nuc-1 ced-4, ced-9

31
Q

What are the 4 steps of apoptosis during development?

A

decision (Beschluss), excution, engulfment, degradation

32
Q

how does Engulfment happen?

A
  • No macrophages.
  • Neighboring cell (epithelial) removes cell corpses.
  • two signaling pathways.
  • both activate the small GTPase ced-10
  • ced-10 promotes cytoskeletal rearrangements that lead to engulfment.
33
Q

Outlook: cancer and apoptosis

A

Cancer involves the abnormal accumulation of cells resulting from an imbalance of proliferation and programmed cell death.
different argents: unprimed cells can first be primed, and then compelled to commit to cell death.