Tissue Repair Flashcards
Describe the orientation of the brain along the dorso-ventral axis.
Dorsal = top
Ventral = bottom
Describe the orientation of the brain along the anterior-posterior axis.
anterior = infront
posterior = back
What are the 3 components of the brain and their relative size and location.
forebrain = very big, covers everything
midbrain = small, wrapped inside by forebrain
hindbrain = medium, underneath everything
in embryonic brain, what is midbrain and hindbrain called?
- mesencephalon = midbrain
- metecephalon = hindbrain
Describe the mid brain patterning structure including notochord and isthmic organisor
- notochord = running along posterior to anterior, underlies almost entire axis
- isthmic organisor sits between midbrain and hindbain
Where is the roof plate and floor plate located?
dorsal = roof
ventral = floor
Explain the dorso-ventral patterning of the neural tube.
- notochord lies under ___along axis
- patterning of neural tube receives ____
- both notochord and fp secretes the ___
- floor plate
- signals
- shh
State the different neuron subtypes produced along the dorsal-ventral axis
- dorsal = dorsal root ganglion
- ventral = motor neurons
How is Shh involved in activating gene in the brain?
- main molecule that floorplate abd notochord secrete is SHH
- gradient of SHH from ventral side to dorsal side
- further from source = lower strength of signal (dorsal)
- result = activation of a TF
- high sonic = lots of GLI = activation of a gene
Describe the signal transduction in the OFF state without SHH
- 2 receptors (PTCH1 actively inhibits another receptor SMO)
- GLI is in a repressive state because no sonic is expressed
- the protein that sonic binds to is Patched1
Describe the signal transduction in the ON state with SHH
- sonic binds onto patched1 which derepresses the ability to inhibit SMO
- SMO is free to activate GLI pathway → GLI turned from repressor to activator and turns on genes
Describe the gradient of GLI activation and what it leads to
gradient of reducing sonic = gradient of GLI activation further form floor plate
- different strength of GLI activation leads to different cellular identities
Different genes have different ___ to activation by SHH-GLI pathway
threshold
Cells 1 2 and 3 increase in distance from floor plate secreting shh. Genes have diff thresholds to activation.
___ has low threshold therefore present in ____
___ has high threshold therefore present in ____
Nkx6.1, 1,2,3
Nkx2.2, 1
Olig2 is absent in 1 and 3 but present in 2. what s this due to?
negative feedback and other TFs, transcription factor B (is present) could be a negative regulator of TF C
In midbrain, TF is different. Instead we have FOXA2 as a ____ threshold gene for Shh
medium
Domapinergic neurons make dopamine. What enzyme is expressed in neurons leaving floorplate?
Tyrosine hydroxylase
Lmx1a, Msx1/2 and Nurr and TF expressed in ventral midbrain. Where is each expressed?
- Lmx1a = both floor plate and DA
- Msx1/2 = floor plate but not DA
- Nurr = DA but not floorplate
Msx1/2 is restricted to only being expressed in floorplate. This shows that it requires…
high threshold of Shh
DA/tyriosine hydrolase is not expressed in floorplate. meaning…
as cells leave floorplate they start expressing it, more mature marker of mid brain leaving cells
Nkx6.1 (low threshold gene) is in mid brain it is repressed in floorplate. It is in lateral region but not floorplate in midbrain showing that…
it is an inhibitor
In an experiment, all cells are repressed for Pax6 and express Nkx2.2. how to alter so cells express Nkx2.2?
shh can change identity of these cells to be very ventral) dorsal→ ventral just by adding shh
addition of Shh comes on but only in lateral tissue that came from midbrain. what does this show?
smt abt anterior posterior identity of even the lateral tissue that makes it response to sonic (only turn into midbain type cells if lateral tissue came from that position in hind)
What is isO (isthmic organisor)
- organisor = transmits signal to nearby cells
- strip of tissue that separates midbrain and hindbrain
How is isO an organisor?
it is a group of cells that transmit FGF8 to nearby cells that influence their developmental fate
FGF8 creates a ____ that is ___ near the organisor and ___ going down each direction
gradient, highest, lowest
Having the 2 gradients in mind (Shh an d FGF8), how is the ventral, midbrain and hindbrain patterned?
ventral = high Shh
midbrain = FGF8 and medium WNT
hindbrain = FGF8 and high WNT
List the 3 brain diseases and which ones lead to brain shrinkage?
alzheimer’s desease = brain disease shrinks as neurons die
huntington’s disease = dementia, brain shrinking issue
parkinson’s disease = anatomy of brain is normal but specific neuron is dying
Describe what is lose in Parkinson’s disease that leads to motor problems?
DOPA (precursor of dopamine) in striatum
in parkinson’s disease, n__m___d___ n___ are lost
- these neurons supply d____into the putamen in the st_____
- in parkinson’s disease, nigral midbrain dopaminergic neurons are lost
- these neurons supply dopamine into the putamen in the striatum
The following question is about location:
- nucleus of these neurons sit in _____
- end points where axons innervate sits in ____
- substantial nigral
- putamen
What is a way to counteract the effect of DOPA missing?
replace neurons lost by inserting dopamine secreting cells into putamen
What are 2 sources of tissue of dopaminergic neurons for transplantation?
- ventral midbrain tissue from human foetus
- midbrain DA neurons from embryonic stem cells
What is significant about the lesion rat model of Parkinson’s
lesion only one side of striatum (toxin injected to kill half the neurons)
Explain the asymmetric motor deficit in 6-OHDA lesion rat model
- functional test = amphetamine induced rotation assay
- rat has lopsided innervation (lots of dopamine one one side)
- so if rat is injected with amphetamine and put the rat in a cylinder rat will rotate in the rotation of the lesion
What are problems with using metal tissue?
- ethical issues
- poor and unpredictable supply of tissues ]poor quality and heterogeneity of tissue
2 types of pluripotent stem cell:
embryonic stem cells
induced pluripotent stem cells
Why do we want pluripotent stem cells to produce progenitors instead of neurons
so they are transplantable
Lmx1a mature and leave ____making ____ ____(make dopamine) and populate left and right _____
- floorplate
- tyrosinase hydroxilase
- substantial nigral
how to make midbrain floor plate tissue:
- dual SMAD inhibition = ____
- ___ SHH activation = ____
- ___ WNT signal = ___
- ____ FGF8b signal = _____
- anterior neural
- high = ventral
- tuned. = caudal
- timed = midbrain
What is CORIN?
cell surface marker only expressed in floor plate
