Boundaries in Development Flashcards
when do tissue boundaries form?
boundaries form when two different tissues in an embryo abut each other
tissues may not be morphologically different but will be molecularly (i.e. expressing different genes)
significance of tissue boundaries? (4)
establishing tissue during embryonic development
maintaining tissue organisation in adults
establishing signalling centres - often at tissue boundaries
disruption of tissue boundaries can lead to disease
give an example where disruption of tissue boundaries can lead to disease
tumour metastasis - tumour malignancy progresses as boundaries are lost & tumour cells spread into healthy tissue
what is a selector gene?
a gene which encodes a TF that directs the expression of downstream genes within a specific cell group
- downstream effects of selector genes determine cell identity and behaviour
- ensures cells adopt specific fates & maintain stable boundaries
describe the formation & maintenance of AP compartments in fruit fly wing development through the actions of a selector gene
selector gene Engrailed is only expressed in posterior cells - establishes posterior cell fate
Engrailed has two actions:
1. induces Hedgehog expression
2. represses cubitus interruptus (Gli) = transducer of Hh signalling
Hh expression induced in posterior cells - Hh is secreted as a short-range morphogen & diffuses across boundary to anterior cells near the AP boundary
repression of Gli in posterior cells means that despite Hh presence, there can be no Hh signalling in posterior cells
however anterior cells near the AP boundary have no Gli repression and do have Hh signalling
- induces expression of Dpp = a long-range diffusible BMP molecule
- Dpp spreads through both compartments and creates gradients that control the growth and patterning of the wing disc
list the three mechanisms involved in cell segregation
- differential cell-cell adhesion
- differential cortical tension
- contact repulsion
what is the differential adhesion hypothesis?
cells in a mixed group will organize themselves based on their adhesive properties
cells maximize contact with similar cell types and minimize contact with dissimilar types – leads to organized cell patterns within multicellular tissues
- higher adhesion = clustering
- lower adhesion = promotes boundary formation
what are cadherins?
adhesion molecule transmembrane proteins - promote cell-cell adhesion through homophilic (same cadherin type) interactions
how do cadherins promote cell-cell adhesion?
binding to the same cadherin type on adjacent cells (homophilic binding) - strengthens attachment
their cytoplasmic domain links to the actin cytoskeleton = reinforce cell-cell junctions
what happens if cells with the same cadherin levels and types are mixed together?
cells mix evenly, create a salt and pepper distribution
what happens if cells with different cadherin levels, same type are mixed together?
cells with higher cadherin levels cluster centrally due to stronger adhesion
lower-cadherin cells remain on the periphery
what happens if cells with different cadherin types are mixed together? how does this support DAH?
cells expressing distinct cadherin types segregate with strong boundaries between them
- have weak affinity towards each other
- minimise contacts and form distinct boundaries
- supports DAH
for what mechanism of cell segregation does the differential adhesion hypothesis apply?
differential cell-cell adhesion
what is the role of cortical tension?
minimises surface energy between different cell populations in tissues
encourages cell segregation & straight boundaries – reduces energy in multicellular tissues
describe the molecular basis of cortical tension
depends on a balance between cadherins & actomyosin contraction
cadherins
- bind cells of the same type together
- form large compl`exes that connect to the cells’ cortical actomyosin networks
- ensure cell-cell adhesion with contractile forces
actomyosin contractions & network formation powered by myosin II leads to myosin II light chain phosphorylation & contraction
- increases cortical tension
cortical driven by actomyosin contraction reduces contact areas BUT cadherins expand contact areas
- balance results in straight, stable boundaries between cell types`
