Tissue repair Flashcards
What structures of the anterior-posterior CNS develop into?
Hindbrain=cerebellum
midbrain=mesencephalon
Forebrain= telencephalon and hypothalamus
What does the dorso-ventral CNS look like?
Has a floor plate (ventral) and roof plate (dorsal) and somites on either side
motor neurons are ventral
dorsal root ganglion are dorsal
How do the floor plate and notochord influence patterning?
The notochord and floorplate secrete SHH which influences ventral tissue formation. The Shh RNA only expressed in notochord, but forms protein gradient in floor plate
Highest in floorplate, the more dorsal it gets the lower Shh levels get
Explain the SHH pathway
PTCH1 represses SMO by binding its receptor, SHH binds PTCH1 and moves it so SMO can bind and activate GLI expression. GLI has same expression gradient as Shh.
How does Shh gradient induce so many different expressions?
Due to threshold genes have.
Low threshold= dont need much signalling (eg Nkx6.1 is turned on by the smallest amount of Shh)
High threshold= need lot of signalling (eg Nkx2.2 needs a lot of Shh)
How are medium threshold genes regulated?
- repressors/activators
- Negative feedback
How is FGF8 secreted in the nervous system?
The isthmic organiser secretes it anteriorly and posteriorly, and can change the cell fate of surrounding cells. FGF8 is the most concentrated next to IsO.
Parkinsons treatment
Dopaminergic neurons are located in the striatum. Can transplant fetal ventral midbrain tissue or midbrain DA neurons from hESCs.
What does high Shh induce?
Ventral tissue, as seen by Nkx2.2 expression when cultured with high Shh, and Pax7 expression (dorsal marker) when cultured in no Shh
What are the different DA TF and where are they found?
DA progenitors (TH) and TF only found in midbrain tissue when exposed to HIGH Shh
Msx1/2 is expressed only in floor plate
Lmx1a is expressed only in floor plate and DA neurons
Nurr1 is expressed only in DA neurons
How do FGF8, Wnt, and Shh influence nervous tissue?
High Shh= ventral tissue
FGF8 + medium Wnt= midbrain tissue
FGF8 + high Wnt= hindbrain tissue
How are DA neurons made from hESCs/iPSCs
Both seperate into the three germ layers, take the ectoderm and isolate it. Apply Dual Smad inhibition, inhibit BMP, and activin/TGFb) to induce primitive neurons. Then apply floor plate protocol (High Shh, medium Wnt, and Fgf8)
In parkinsons
Explain the 6-OHDA lesion rat model
6-OHDA kills neurons and create a lesion on one side of the striatum. Results in rat running around in circles. Transplant 9 week old fetal midbrain corrected this asymetry. hESC/iPSC DA neurons work in this model too.
