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 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
how does the AP boundary int he wing imaginal disc of fruit flies become an important signalling centre
Ap boundary direct cell fates, cellular organisation across wing imaginal disc and influences adult wing structures
Hh expression from most posterior cells to anterior cells near the AP boundary as a short-range molecule & Gli repression (both induced by selector gene Engrailed expression in posterior cells) - specifies anterior fate in those cells near the AP boundary that can respond to Hh signalling
AP anterior cells release DPP as a long-range BMP morphogen - signalling centre/source that influences differential gene expression across both compartments through morphogen gradients
list the three mechanisms involved in cell segregation
- differential cell-cell adhesion
- differential cortical tension
- contact repulsion
what is the differential cell-cell 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 differential adhesion hypothesis
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
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 complexes 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
what is the role of myosin II in boundary precision with cortical tension?
there is higher cortical tension at boundaries where myosin II is active
- strengthens cell type separation
myosin II dependent cortical tension is important for straight boundaries & restricting cell mixing
what is the effect of myosin II mutations?
mutations disrupt cortical tension = fuzzy borders and more cell mixing
what is the role of contact repulsion?
stops cells from intermingling at boundaries between diff cell types
maintains clear divisions between diff cell populations
what is contact repulsion dependent on?
Eph-ephrin signalling
how is Eph-ephrin signalling important in boundary formation?
Eph-ephrin signalling is important for contact repulsion
- Eph receptors on one cell bind ephrin ligands on a neighbouring cell = induce bidirectional signalling
- Eph-ephrin interactions increase actomyosin contraction in boundary cells
- increases cortical tension; weakens cadherin-based adhesion
- increased tension and reduced adhesion causes cell repulsion = stabilises boundaries, with no cell mixing
how does Eph-ephrin signalling affect cortical tension and cadherin-based adhesion?
cortical tension increases
cadherin-based adhesion decreases
this is because Eph-ephrin interactions increase actomyosin contraction in boundary cells
how does Eph-ephrin signalling and ephrins promote cell repulsion?
Eph-ephrin interactions increase actomyosin contractions in boundary cells
cortical tension increases
cadherin-based adhesion decreases
induces cell repulsion
describe selector gene expression that defines the midbrain-hindbrain boundary
Otx2 is expressed anterior to the MHB - defines midbrain identity
Gbx2 is expressed posterior to MHB - defines hindbrain identity
- mutual repressions between Otx2 and Gbx2 maintains stable boundaries as the neural tube develops, prevents cell movement across the boundary
