Casson (Developmental genetics) Flashcards
How much complexity must be dev from a single cell?
- ≈10-50 trillion cells of >200 cell types
What diff patterns can form in an organism?
- apical-basal polarity (top and bottom)
- dorsal-ventral polarity (back and front)
- bilateral symmetry (2 mirror halves w/ single plane)
- radial symmetry (division into equal portions from centre)
By what processes does 1 cell generate such complexity?
- cell proliferation –> increase in cellular no. via cell division
- cell specialisation –> cell differentiates to acquire specific cell fate/role in certain position
- cell interaction –> cell behaviour coords w/ that of neighbours
- cell movement –> rearrangement of cells to form structured tissues/organs
In what organisms does cell movement not occur, why and what do they do instead?
- plants
- cells essentially fixed
- so achieve dev by regulated division pattern
What would happen if cell divides w/o specification?
- get clones, so never get any differentiation
How can 1 cell give rise to diff daughter cells w/ diff identities through intrinsic asymmetry?
- DIAG*
- component becomes polarised in mother cell prior to division
- unequal distribution leads to daughter cells w/ diff fates
- not always physical asymmetry of division –> can both be same size but contain diff determinants
How can 1 cell give rise to diff daughter cells w/ diff identities through extrinsic asymmetry?
- DIAG*
- diff fates gen by signalling between cells, from surrounding cells or from precursor cell
- signalling only acts upon 1 cell
When does asymmetric division occur?
- often at v beginning of embryo dev, when fertilised egg divides to give daughters w/ diff fates
- in assoc w/ stem cells (in animals and plants), where division regens daughter w/ stem cell activity and 2nd daughter w/ new fate
How does extrinsic asymmetry cause diff fates to occur?
- lateral inhibition
- DIAG*
- 2 cells both inherit determinant x after cell division
- x acts on neighbouring cell to inhibit prod of x
- transient bias creates slight symmetry –> stochastic
- +ve feedback amplifies diff
- bistability –> all or none alt outcomes, gen opposite but relatively stable states
How can short range cell-to-cell signalling quickly gen increased complexity w/in a dev tissue?
- DIAG*
- B signals to A, resulting in new cell type C being specified
- C signals to A and B, to gen D and E, respectively
Do cell autonomous decisions occur too, and when?
- yes
- examples where cells in culture undergo specific no. divisions before differentiating
- but much harder to prove in an in vivo cellular env
What is a morphogen?
- signalling molecule that acts directly on cells to prod specific cellular responses, dep on its local conc
What type of molecules can morphogens be?
- TFs
- hormones
- signalling molecules
How do morphogens gradients work?
- morphogen prod in 1 region and diffuse from source creating grad
- responses w/in grad occur at threshold levels
- so cells acquire diff fates dep where lie in conc grad
- DIAG*
How can morphogen grad be represented as a circle?
- DIAG*
- greatest conc at centre
- decreases as diffuses outwards
How can morphogen activity be key to output, instead of conc?
- DIAG*
- morphogen uniformly distributed
- inhibitor has conc grad
- inhibitor interacts and -vely regulates morphogen activityU, resulting in opp grad of morphogen activity
Using an inhibitor to control morphogen activity is more complex than a conc gradient, so why bother?
- sometimes may wish to limit activity of morphogen and this allows more control than just relying on morphogen distribution
If morphogen is a TF, what would we expect expression pattern to look like for a gene w/ high or low affinity, across a changing morphogen conc?
- high = activated fairly evenly across whole domain , as sites bound even at low concs of morphogen
- low = when morphogen conc decreases, expression quickly turned off
What functional classes of genes is early Drosophila dev dep on?
Axis formation:
- egg-polarity genes
Segment identity:
- gap genes
- pair-rule genes
- segment polarity genes
Why couldn’t segment identity gene expression in Drosophila be reg by other zygotic factors?
- 1st turned on when zygotic transcrip initiates
- must be factors already present in zygote to direct their expression
How did Nusslein-Volhard carry out a mutant screen which resulted in identification of several maternal effect genes?
- looked for mutant phenotypes in progeny of females from a homozygous mutant pop
- as females defective in maternal effect gene dont show mutant phenotype, as from egg form heterozygous female, but offspring do
What general effect do mutations in maternal effect genes have on Drosophila dev?
- large scale deletions of body plan
What is the structure of a WT Drosophila embryo?
- DIAG*
- acron, head, thorax, abdomen, telson
What are the diff phenotypes of Drosophila w/ mutations in maternal effect genes?
- bicoid –> deletions in anterior region (head and thorax)
- nanos –> deletions in posterior region (abdomen)
- torso mutant –> terminal deletions