Flashcards in CellSig9 - 13 Deck (13):
Induce different outputs at different concentrations and act directly at a distance
What are the two theories about morphogenetic signals?
Instructive and permissive
Are morphogenetic signals instructive or permissive?
How do you distinguish between instructive or permissive signals?
Provide a second source - instructive leads to mirror image, permissive leads to no effect; provide constant signal - instructive leads to only one cell type, permissive has no effect
How do you distinguish between acting at a distance and bucket brigade?
Make the morphogen a juxtacrine, locking it in the membrane - direct at a distance would only affect the adjacent cell, bucket brigade would not be affected; remove the receptor in one of the cells - direct at a distance only that cell would not differentiate, bucket brigade would not be affected
Is passive diffusion what establishes a morphogen gradient?
No - it'd be too shallow a gradient; ligand binds to ECM elements like heparan sulphate proteoglycans to generate restricted diffusion and rapid degradation helps
What are HSPGs sometimes known as?
Co-receptors - they sequester, slowing or facilitating diffusion
How else do morphogens travel, other than facilitated diffusion?
Planar transcytosis - repeated cycles of endocytosis and resecretion
What morphogens are associated with planar transcytosis, and how do we know?
Dpp signalling - antibody staining reveals localisation in vesicles, and blocking of vesicle formation leads to Dpp being juxtacrine only
Why is timing an important factor in establishing morphogen gradients?
Gene expression must change over time due to the change in gradient, but there must be a mechanism to block premature expression - this is poorly understood
How are strict thresholds established in morphogenetic patterning?
Transcription read-out model - response based on number of transcription factors, which is dependent on morphogen concentration
How is TF concentration interpreted at the DNA level?
All about affinity - high affinity to low concentration leads to outcome A, low affinity to low concentration leads to outcome B