What is induction?
- Changes in cell fate due to signals sent from other cells
What is embryonic induction?
- Specifically refers to this process of induction during embryonic development; one tissue sends signals to direct development of another tissue
What factors can affect how a cell responds to an inductive signal:
- Combinatorial signalling- other signals the cell is currently receiving
- Cell memory (previous effects of other inductive signals- often reflected in chromatin marks)
What is a morphogen?
- a secreted, diffusible protein molecule that can influence the fate of a field of neighbouring cells via a concentration gradient
What is a morphogen gradient?
- The concentration of a morphogen is highest in closest proximity to the morphogen secreting cell and decreases with distance. The cells closer to the morphogen secreting cell receive a higher concentration ‘dose’ of the morphogen. Once a morphogen concentration goes albove/below a specific threshold a different gene may be affected.
What is lateral inhibition and what kind of signalling does it use?
- Lateral inhibition is a type of inductive signalling in which cells send inhibitory signals to neighboring cells.
- It often uses the delta-notch signalling pathway.
What is the delta-notch signalling pathway?
Ligand(s): Delta, jagged or serrate
Receptor: Notch
- Involves the direct interaction between delta and the notch receptor
- The delta ligand of the signalling cell binds to the Notch receptor of the neighbouring cell, this activates an intracellular protease which cleaves part of the intracellular domain of Notch which translocates to the nucleus where it triggers the transcription of certain genes
How do reaction-diffusion systems generate patterns?
- Positive feedback and lateral inhibition mediated by diffusible substances over a broad range of cells generate patterns in the embryo
- e.g. a short range activator in once cell will stimulate its own production in that cell; once a sufficient number of neighbouring cells have been developed to a certain fate determined by that activator; the cells will release a long range inhibitor to block the production of the activator by other cells in the neighbourhood to stop them developing the same way
Explain autocrine signalling:
- A cell releases signalling molecules to target itself
Explain paracrine signalling:
- short range signalling between neighbouring cells
- the most common type of signalling used during embryonic development
Explain endocrine signalling:
- long range signalling from one part of the body to another
What are the 4 main families of paracrine signalling pathways used in development?
- Fibroblast growth factors
- Hedgehog
- Wnt
- Transforming growth factor-B
How does fibroblast growth factor signalling work?
- Uses a receptor tyrosine kinase
- When the FGF binds the receptor tyrosine kinase the receptor phosphorylates itself and triggers a cascade of phosphorylation events leading to the phosphorylation of ERK which phosphorylates transcription factors in the nucleus
How does transforming growth factor beta (TGF-B) signalling work?
- Uses a serine/threonine receptor
- Binding of TGF-B to the receptor results in the receptor undergoing dimerisation and activation leading to it becoming phosphorylated and a phosphorylation cascade leading to the phosphorylation and activation of Smad proteins which go onto target gene expression.
How does the Wnt signalling pathway work?
- Uses LRP and Frizzle receptors
- When Wnt is not bound to receptors the intracellular protein B-catenin is being constantly degraded by a destruction complex
- When Wnt binds it dimerises the LRP and Fz receptors which causes the destruction complex to become sequestered and B-catenin is stabilised and no longer degraded
- B-catenin then enters the nucleus to target gene expression
Describe how hedgehog signalling works:
- Uses patched receptor (PTC) which interacts with smoothened receptor (SMO)
- Hedgehod signalling molecule leaves the signalling molecule and binds to PTC and the activated PTC interacts with SMO so SMO is no longer inhibited and GLI3 transcription factor is no longer degraded
- GLI3 transcription factor enters the nucleus and affects target gene expression
Match the signalling molecules to their receptors:
- Transforming growth factor-B
- Fibroblast growth factor
- Wnt
- Hedgehog
- Receptor tyrosine kinase
- Receptor serine/threonine kinase
- LRP and Frazzle receptors
- Patched receptor and smoothened receptor
How does retinoic acid signalling work?
- Vitamin A from diet enters cells and is converted to retinoic acid by the RALDH enzyme
- Retinoic acid is degradaded by CYP26 enzyme
- The synthesis and degradation of retinoic acid must be in balance as retinoic acid enters the nucleus and can influence target gene expression
- Too much retinoic acid (e.g. due to the deletion of the gene encoding CYP26) leads to body abnormalities such as a lack of posterior region formation
What is morphogenesis?
- the organisation of form; groups of similar cells forming tissues
- often regulated by cadherins
What is a cadherin?
- calcium binding adherin molecules; different types and amounts influence how cells adhere to eachother
