we observed BMP expression in bulb and bulge area after a drug treatment and also Beta-catenin expression did not increased in bulge or bulb in comparison to control. Moreover we cant conclude about this results. could you help me?
also, we showed that Kras/Erk1 signaling pathway is activated and Shh gene expression were increased. Among the BMP, Kras/ERk1 and Shh, it is Shh that over expressed in bulb and bulge.
it seems that Kras/ erk1 signaling pathway correlated with cell survival, and also Shh over expression indicative of cell survival in bulb and bulge, but when we did not see beta catenin over expression, if can we conclude the drug caused anagen or cell survival after 7 day drug treatment?
This seems straight- forward. The basic rule in the rodent hair follicle is that BMP signaling (probably most likely BMP2 and/or 4) inhibit hair growth while canonical Wnt signaling induces and maintains hair growth. There are many details to it since even a mouse hair follicle is a complicated structure with many cell types and levels of differentiation.
So, in creased levels of BMP (which one) should lead in many hair follicles to catagen induction or inhibition of anagen. Your statement that you don't see b-catenin is strange. What do you mean? Loss of nuclear beta-catenin or an overall loss/reduction? A loss of the nuclear expression makes sense since it is an indicator for anagen induction or quasi hair shaft production depending on which cell type you look at in the hair follicles and at which time point. if there is no or inefficient anagen induction where will be problems downstream and no or far less beta-catenin in the bulb/hair cortex area will appear. a little bit of yin and yang here.
You may get very messy hair follicles depending when you inhibit canonical Wnt signaling. If you do it at or before anagen onset and the treatment is effective you may just get an arrest in telogen. if the hair follicle makes it into anagen with messy levels of canonical WNT signaling things may get ugly may be ending with the destruction of the hair follicle, cysts. Hard to say.
What can you conclude? Depends on the details. What exactly is the outcome, for example when the drug is applied around postnatal day 18, before the fist postnatal hair growth cycle (in most untreated mouse strains). Depends whether where is loss of all beta-catenin (in my opinion virtually impossible) or "just" nuclear beta-catenin. Depends how the drug effects hair follicle in anagen itself: does it lead to severe aberrations in hair shaft production and a "mechanical" failure resulting in the loss of a normal hair follicle structure? Basically: do you get a phenotype similar to a beta-catenin knockout or of Dkk1 overexpression?
Hair follicle stem cells (HFSCs) and transit-amplifying cells (TA cells) exist in the bulge and bulb region, respectively. It has recently been reported that the response to BMP ligand depends on the following two conditions; Firstly, the differentiation status between HFSCs and TA cells, and secondly, in which the hair cycle stage cells participate (anagen, telogen, catagen in 1 month). Given that there is a cross-talk between BMP and canonical Wnt signal pathways, phosphorylated SMAD1/5 is likely to negatively regulate the beta-catenin accumulation in the nucleus. Why not perform IHC with ID-1 or p-SMAD1/5 ?
Ref.
BMP Signaling and Its pSMAD1/5 Target Genes Differentially Regulate Hair Follicle Stem Cell Lineages.
Genander M, Fuchs E, et al
Cell Stem Cell. 2014 Oct 8. pii: S1934-5909(14)00400-7. doi: 10.1016/j.stem.2014.09.009.
- Badges
- Science topic
- Similar topics
- Comment