Tanycyte specification Flashcards
+ establishment of a hypothalamic stem cell niche
What are tanycytes derived from?
- tuberal gliogenic cells
- derive from the sustained pSmad1 and FGF10 signalling
What do tanycytes form?
The median eminence
What can transcriptional profiles tell us about how differentiation changes over time in relation to tanycyte specification?
- In the last few transcriptional profiles taken over time, new genes are suddenly upregulated e.g. Sox8, Sox9 etc
- These genes upregulated towards the end are the ‘characteristic’ genes of radial glial cells (step before tanycyte)
What is so special about radial glial cell?
- Stem-like properties
- can form different cells within the differentiation of neurons in the spinal cord and can self renew
What is the lineage from Tuberal progenitors to tanycytes?
Fate mapping has shown the lineage from tuberal gliogenic → radial glia → tanocytes
How are radial glial cells located around the third ventricle (where median eminence is)?
- Radial glia cell bodies are located at the lumen (Ventricular zone/lumen of the third ventricle)
- The ends tend to extend to the Arch nucleus
What can be generated from tanycytes?
- Neurons can be generated - form Arch nucleus which are fundamental in energy homeostasis and reproduction
How have experiments found that Tanycytes proliferate in response to FGF10?
- In an experiment, FGF was introduced into the brain, and a thymidine analog (a marker for DNA synthesis) was used to track cell replication.
- When FGF was added, more thymidine analog was incorporated, indicating increased proliferation of tanycytes due to the stimulatory effect of FGF on cell division.
How do we know tanycytes are stem cells?
- Tanocytes can be labelled with conditional lineage tracing using Cre-lox (GLAST:CREERT2) and tamoxifen system
- In an experiment, tanycytes are initially the only cells labelled
-After nine months, tamoxifen is reapplied to visualize the marker, and a variety of different cell types are observed: astrocytes, alpha and beta tanycytes and neurons - Tamoxifen was also applied at 5 days and 6 week to observe but 9 months was the significant change
- Shows stem cell characteristics
When are the majority of tanycytes generated by in mice?
E15 - end of neurogenesis
What do some studies suggest that stem cells are stimulated by?
- Studies suggest that stem cells in the hypothalamic environment are stimulated by signals from neurons.
-Release of factors that regulate proliferation and differentiation, highlighting a dynamic interaction between neurons and stem cells in maintaining hypothalamic function.
Why may tanycytes be really important in disease and why?
- Role in homeostasis - idea that loss of hypothalamic neurons & circuits/function is a key event leading to type 2 diabetes
- Due to tanycytes role in actively transporting ghrelin and leptin across the blood brain barrier
What experiment has been conducted to link tanycytes with Type 2 diabetes?
- Paper shows specialised glial cells lining 3rd ventricle respond to injected FGF1 by expressing heat shock protein 25
- This potentially displays a role in glucose regulation as it let to sustained remission of diabetic glycaemia in rodents
What is the niche that stem cells need to grow?
Progenitor cells
Support cells
Endothelial capillaries
How do the capillaries grow for stem cell niches?
FGF guidance involved in the capillaries
Capillaries (red) surround the endfeet of the neurons (green)
In a FGF mutant in fish, you dont have the capillary system which shows that FGF is needed in capillary guidance
