L12-neurodegeneration Flashcards
what is another name for motor neuron disease?
Amyotrophic lateral sclerosis
ALS
what happens in motor neuron disease?
motor neurons die
- this causes muscle weakness and wasting
- causes death due to defects in muscles that help you to swallow and breath
how can motor neurons be made from a stem cell/
- stem cells taken from inner embryonic mass and form embryoid body
- embryoid body induced to a neural fate (BMP antagonists?)
- posteriorization (RA)
- ventralisation to MNs (Shh concentration)
what are the markers for differentiated motor neurons?
Isl1 and HB9
what are the markers for motor neuron progenitors?
Nkx6.1, pax6 and olig2
what is a marker for posteriorised neural cells?
Hoxc6
what did jessel et al do?
showed it was possible to produce motor neurons from embryoid bodies
what are the problems with being able to show that MNs behave properly when transplanted back into host spinal cord?
- need a pure population of MNs to transplant back (usually multiple ventral neurons due to different Shh concentrations
- have to be able to identify and follow transplanted MNs when in the host
what is the reporter line used to identify motor neurons?
HB9;eGFP
how is a pure motor neruon population made?
- ESCs taken from mouse and put back in HB9;eGFP
- male and female progeny of this mouse bred together
- can see MNs as floresce green
- facs sorting isolates green cells/MNs
-create transgenic mouse and remove scs from innercell mass- can identify differentiating motor neurons and purify via facs
how do transplanted motor neurons act when transplanted back into host?
-in the chick the motor neurons integrate into the spinal cord and take on normal axon trafectories associated with normal motor neurons
what is the long term goal we want to achieve in order to help us treat MDN?
- want to push human pluripotent stem cells to a motor neuron fate ex vivo
what mutations can be linked to MND?
mutations in SOD
