WNT DKK

[hedgehog_info]

WNT and DKK Determine Hair Follicle Spacing Through a Reaction-Diffusion Mechanism.

Mathematical reaction-diffusion models have been suggested to describe formation of animal pigmentation patterns and distribution of epidermal appendages. However, the crucial signals and in vivo mechanisms are still elusive. Here we identify WNT and its inhibitor DKK as primary determinants of murine hair follicle spacing, using a combined experimental and computational modeling approach. Transgenic DKK overexpression reduces overall appendage density. Moderate suppression of endogenous WNT signaling forces follicles to form clusters during an otherwise normal morphogenetic program. These results confirm predictions of a WNT/DKK-specific mathematical model and provide in vivo corroboration of the reaction-diffusion mechanism for epidermal appendage formation.

* Present address: Novartis Institutes for Biomedical Research, Basel, Switzerland.

Originally published in Science Express on 2 November 2006
Science 1 December 2006:
Vol. 314. no. 5804, pp. 1447 - 1450
DOI: 10.1126/science.1130088


Its all there Wnt & Hh

Cheers

 

[So]

What does this mean? Elaborate.

 

[hedgehog_info]

What does this mean? Elaborate.

Hi So,

I guess a simple answer is that the researchers think they found a mechanism for hair follicle spacing on the mouse.

There are a couple vital a key morphogenic embryonic pathways. Wnt, Hh, and BMP's are just a few of them. Morphogen's are signals (proteins and or molecules) that effect the cell based on their concentration. In the article above it states the higher the Wnt protein concentration is the more hair follicles develop. It should also been known that the Wnt pathway also helps the hair follicle develop direction and grow the hair in the proper direction.

Hh is the key protein to kick that new hair follicle into the growth phase.

Try to google "Wnt" and "hair"

 

[Apoc]

Hooray for mice. Tough luck for us humans. Mice will probably be able to live for a million years with all the scientists working on their problems.

 

[Armando Jose]

Is there any contradiction between the two statements?
"In the article above it states the higher the Wnt protein concentration is the more hair follicles develop."
And "Moderate suppression of endogenous WNT signaling forces follicles to form clusters during an otherwise normal morphogenetic program"

OTOH, Hh is the key protein to kick that new hair follicle into the growth phase, and, what happen in the other phases of hair, are suppresed it??

TIA

Armando

 

[hedgehog_info]

Is there any contradiction between the two statements?
"In the article above it states the higher the Wnt protein concentration is the more hair follicles develop."
And "Moderate suppression of endogenous WNT signaling forces follicles to form clusters during an otherwise normal morphogenetic program"

I don't think so it just means that the source cells of the Wnt protein only develop hair follicles because of DKK is applied at higher concentrations. For example if you have cells A B C D that are expressing the Wnt protein and then you use an inhibitor of Wnt the only cells that are going to feel the effect are the very closest cells. This is why you get the clumping.

OTOH, Hh is the key protein to kick that new hair follicle into the growth phase, and, what happen in the other phases of hair, are suppresed it??

yes it kicks new and old hair follicles into the growth phase. Nobody really knows about the other phases and how it is suppressed. However, I do know that a plausible mechanism is that the Hh pathway actually has a negative feed back system which turns itself off after a period of time.

 

[DaSand]

Wouldn't you have to use this again and again when the follicles are again suppressed by DHT?

 

[hedgehog_info]

Yes you would have to apply a Hh agonist treatment every few years. However, it really depends on how fast it falls out.

 

[Armando Jose]

Thank you for your explanation, but

Quote:
OTOH, Hh is the key protein to kick that new hair follicle into the growth phase, and, what happen in the other phases of hair, are suppresed it??


yes it kicks new and old hair follicles into the growth phase. Nobody really knows about the other phases and how it is suppressed. However, I do know that a plausible mechanism is that the Hh pathway actually has a negative feed back system which turns itself off after a period of time.

I concur with your idea, in these case the signal can not be for ever, but, This period of time you say will be several years or only days?

Armando

 

[hedgehog_info]

I concur with your idea, in these case the signal can not be for ever, but, This period of time you say will be several years or only days?

The pathway is only turned on for a day(or less) in order to start the wave of 2ndry pathways to start the hair growing.

If the pathway is turned on to continuous you will get Basal Cell Carcinoma (skin cancer), or if it turned on more frequently then normal you might get a mole with a long hair sticking out of it.

 

[Armando Jose]

Thank you for your response.

Then, it could be easy develop "problems" if we put too much of this signal.

Armando

 

[hedgehog_info]

Yes if you turn on the pathway to much you could develop a lot of problems. Curis/P&G have not noted any side effects after 1 year of a one time topical application treatment. But there is a big chance for side effects and should not be taken lightly.

For example this is not going to be an over the counter answer to for hair growth. It WILL work for hair growth but we will see what the FDA will say.

Not trying to pessimistic but there are some REAL things to consider. I hope it works and I think P&G developing this says a lot and bodes well for clinical trials.


Agonists of the Wnt pathway probably won't be used for Hair growth unless they are using Embryonic stem cells to create new hair follicles.