What is endochondral ossification?
The replacement of a cartilage model by bone.
What causes mesoderm to differentiate into mesechyme?
The apical ectoderm ridge (AER) - this induces proliferation and differentiation of mesenchyme.
Which part of the mesoderm gives rise to the mesenchyme involved in endochondral ossification?
Somatic lateral plate mesoderm.
What are the three stages of signal transduction?
- Detect
- Transduce
- Respond
How do intracellular receptors affect a response?
- hydrophobic molecule passes into cell via plasma membrane
- then binds to sepcific intracellular receptor
- ligand-receptor complex can pass into nucleus and alter gene transcription/protein synthesis
What is an example of a molecule which uses intracellular receptors?
Steroid hormones e.g. oestrogen and testosterone
How does ion gated channels work?
- may be voltage gated or ligand gated
- either mebrane potential of binding of ligand will ‘open’ the gate
- this creates a channel through which ions can flow into the cell
What is an example of a molecule which uses an ion gated channel?
Glutamate neurotransmitter
How does a G protein coupled receptor work?
- ligand binds to receptor (extracellular)
- G protein binds to receptor (intracellular)
- G protein activates enzyme
- ezyme carries signal further into the cell
Give an example of a molecule which uses a G protein coupled receptor.
Adrenaline
How do enzyme linked receptors work?
- ligand binds to receptor (extracellular)
- intracellular region of receptor has enzymatic activity or is associated with an enzyme
- once activated by ligand the enzyme triggers a response
What are a key subtype of enzyme linked receptors?
Tyrosine kinase receptors
Give an example of a molecule which will use an enzyme linked receptor.
Many growth factors
List the different types of cell receptors.
- intracellular
- ion gated
- G protein coupled
- enzyme linked
What are the 2 main methods for signals to be transduced/amplified?
- Enzyme cascades e.g. MAP kinase cascade follows on from many growth factors
- Second messengers e.g. cAMP
What is an oncogene?
A gene whose product is involved in inducing cancer. Most oncogenes are mutated forms of normal genes (proto-oncogenes) involved in the control of cell growth or division.
Explain how a mutation can cause pituitary and thyroid adenomas.
- somatic point mutation of R201 or Q227 inhibits GTP hydrolysis
- constitutive activity mimics signal from hormones that stimulate proliferation and secretion in these glands
How would a deletion/point mutation affect a protein?
Hyperactive protein made in normal amounts e.g. FGFR3 glycine replaced by arginine
How does a regulatory mutation affect proteins?
Normal protein greatly overproduced
How does gene amplification impact a protein?
Normal protein greatly overproduced
How does chromosome rearrangement affect the protein?
- nearby regulatory DNA sequence causes normal protein to be overproduced
- fusion to actively transcribed gene produces hyperactive fusion protein
What is achondroplasia?
A commonly encountered form of exteme short stature where poor bone growth results in shortened limbs.
List some characteristics of achondroplasia.
- near normal trunk length with shorted arms and legs
- large head with prominent forehead and flattened bridge of nose
- increased curvtature of lower spine (lumbar lordosis)
- bowing of lower legs
- possible crowded teeth
- short, broad feet and hands with separation between middle and ring finger
- exceptionally flexible joints
- babies motor and mobility skils may develop more slowly but ultimately development is within normal range
What is the inheritance pattern of achondroplasia?
- 80% are de novo ie not inherited from parents
- 20% are autosomal dominant
