W4

Question 1

Ways of cell signalling.

Answer 1

1. Paracrine factors (diffusable signals) - can act over long distances. 2. signals deposited into extracellular matrix (ECM) - can be long lasting 3. Contact (cell-cell adhesion molecules, gap junctions - high spatial precision.

Question 2

What has the invariable cell lineage and fate map of c. elegans revealed?

Answer 2

Programmed cell deth - apoptosis - analysed. genes involved identified.

Question 3

What are the apoptosis genes?

Answer 3

Caspases in crucial for apoptosis. - they cleave a number of cellular proteins and bring about cell death. Regulated by a number of homologous genes - EGL-1, CED-9, CED-4.

Question 4

What are the genes which control timing of development processes (discovered in C. Elegans)

Answer 4

heterochronic genes, e.g. lin-14, loss of function mutant causes stage 1 of development to be skipped. or lin - 4 and Lin-14 gain of func causes repetition of L1 pattern.

Question 5

What is the Lin-4 / Lin-14 relationship?

Answer 5

Lin-14 is repressed by Lin-4 through mi-RNA mi-RNA as regulator of expression very common in eukaryotic kingdom

Question 6

What are si-RNA?

Answer 6

Short interfering RNA deactivates mRNA by cleaving.

Question 7

What is mi-RNA?

Answer 7

micro RNA deactivates expression by binding to a target mRNA (usually in the 3’ untranslated region) or degrates the bound target mRNNA

Question 8

What control mechanism are responsible for the invariable cell fate of C. Elegans?

Answer 8

Both mosaic-type control and regulation control.

mosaic type: P granules are asymmetrically segregated during the first four cleavage divisions. P granule segregation correlates with germ cell fate. Laser ablation of P4 led to the production of larvae with no germ line. At least one known component of P
granules (PGL-1) is required for germ cell development. P granules function as germ line fate determinants.
The par genes (par: partition, par 1-6) are required for asymmetric segregation of the P granules during the early cleavage divisions. Homologous genes are also involved in establishment and maintenance of cell polarity in other metazoans.

regulative type: ABa versus ABp development

Question 9

What are the two theories of development from the 1800, and the experiments which supported them?

Answer 9

Weismann’s theory of nuclear determinants (mosaic) supported by Roux Regulative Driesch - complete organism still grows despite ablation of cells in early stage.

Question 10

What is an example of regulative development in C. elegans?

Answer 10

The induction of ABp identity by P2 P2 expresses GLP-1 (Notch homologous). Both ABa and ABp have APX-1 receptors (Delta family). When ABp is killed, ABa is adjacent to P2. and takes on the identity of ABp

Question 11

Overview of C. elegans vulva development

Answer 11

1. creation of the vulva equivalence group (six cells P3p, P4p,….P8p 2. induction and lateral inhibition: specification of primary, secondary and tertiary cells. 3. Cell proliferation 4. Morphogenesis

Question 12

Which cells in C. elegans vulva development are primary, secondary and tertiary?

Answer 12

Primary: P6p Secondary: P5p and P7p Tertiary: Pep, P4p and P8p (these have a non-vulva fate)

Question 13

What cell is responsible for determining the fate of the C. elegans vulva cells?

Answer 13

Anchor cell

Question 14

What is the signalling pathway which generates the vulva in C. elegans?

Answer 14

1. Lin-3 signal from anchor cell induces P6p to adopt the primary fate.
2. lateral signal from P6p is received by Lin-12/Notch receptor in neighbouring cells. Inhibits them from adopting primary fate. 3. a consecutive signal from the epidermis also represses development into the primary fate, but is overruled by the signal form the anchor cell.

Question 15

What does the Drosophila eye comprise of?

Answer 15

800 ommatidia

Question 16

What does each ommatidia comprise of?

Answer 16

8 photorecepor cells (R1-8) Cone cells secrete the lense Pigment cells provide optical isolation.

Question 17

Overview of eye development.

Answer 17

1. morphogenitic furrow (MF) moves from p to a across the imaginal disc. Single cells are selected in the MF as R8 precursor cells (lateral inhibition involving Notch)

Question 18

How are the cells in the eye determined.

Answer 18

1. R8 signals with Spitz->Torpedo to iduce two R2,5 cells 2. R8,2,5 signal with Spitz->Torpedo R1,3,4,6 3. R1,3,4,6 signal with Spitz->Torpedo to induce cone cells. 4. cone cells signal with Spitz->Torpedo to induce pigment cells 5. R8 signals with Boss>Sevenless to induce a single contacting cell to develop as R7 This is an RTK signalling path

Question 19

Are RTK signals selective or instructive?

Answer 19

They must be selective because exactly the same pathway can produce a differnt outcome.

Question 20

How can an RTK signal lead to different changes to different cells?

Answer 20

The effect of the signal depends on a cells developmental history and its current state of gene expression.

Question 21

cell death and human health

Answer 21

Aberrations in programmed cell death processes are part of the etiology and/or pathology of many diseases.

• inappropriate inactivation of the death program (cancer, autoimmune diseases, …)
• inappropriate activation of the death program (chronic neurodegenerative diseases, stroke, myocardial heart infarction, …)

Question 22

Not all cell death occurs via apoptosis (execution via caspases)

Answer 22

Alternatives:

• autophagy (self digestions in specialized lysosomes)
• necrosis (cell lysis)
• Wallerian degeneration (after nerve cut)
• various other non-apoptotic cell deaths (plasmid addiction, etc.)

Not all cell death is programmed. While apoptosis with all its characteristic features does not occur in plants, it is very clear that programmed cell death (involving distinct mechanisms) does also occur in plants.

Question 23

heterochrony

Answer 23

genes which control the timing of developmental processes

Question 24

different ways of cell fate diversification

Answer 24

1. asymmetric egregation of fate determinants. e. g. - germ line determination in C.ele. and D. mel. - stem cell renewal in D. mel. neuroblasts
2. lateral inhibition, cell induciton. e.g. - germ line determination in mouse and humans - stem cell renewal in D. mel. ovary - vulva development in C. ele. and eye development in D. mel. are important examples because their analysis allowed for crucial breakthrough towards a molecular understanding of cell-cell interactions in development.

Question 25

induction of VPC fate by a signal from the AC cell: a conserved signaling pathway

Answer 25

RTK pathway (receptor tyrosine kinase)

ligand receptor sets off cascate inside cell which modulates transcription

Question 26

RTK pathways

Answer 26

D. melanogaster Torpedo is homologous to C. elegans LET-23 and mammalian EGF receptor. D. melanogaster Sevenless belongs also to the receptor tyrosine kinase family like Torpedo, LET-23 and the mammalian EGF receptor. Signaling downstream of the activation of all these RTKs involves the same ras/MAP kinase pathway.