Understanding Hair Transplants and Hair Loss - Pacific Hair

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Understanding Hair Transplants and Hair Loss - Pacific Hair

oot sheath and in precursor cells of the hair shaft cortex and cuticle which lie immedi-

ately adjacent to Wnt3-expressing cells.

Millar found that overexpression of Dvl2 in the outer root sheath mimics the short-hair

phenotype produced by overexpression of Wnt3 . This supports the hypothesis that

Wnt3 and Dvl2 have the potential to act in the same pathway in the regulation of hair

growth .

These experiments demonstrate a previously unrecognized role for WNT signaling in

the control of hair growth and structure, as well as presenting the first example of a

mammalian phenotype resulting from overexpression of a Dvl gene and providing an

accessible in vivo system for analysis of mammalian WNT signaling pathways .

Bafico et al., (2001), report that Wnt signaling has an important role in hair follicle

fate determination, tissue patterning and tumorigenesis . Secreted antagonists of Wnt

include Frizzled (Fz)-related proteins (FRPs), Cerberus, Wnt inhibitory factor (WIF) and

Dickkopf (Dkk). FRPs, Cerberus and WIF have all been shown to act by binding and

sequestering Wnt . We report a novel mechanism of Wnt-signaling inhibition by human

Dkk-1 . Dkk-1 demonstrated no interaction with Wnt but bound a single cell surface site

with high affinity (KD=0.39 nM). Its receptor was detectable in a complex with a relative

molecular mass of 240,000 (Mr 240K) with [125l] Dkk-1 by covalent affinity cross-linking

. Wnt signaling through beta-catenin is mediated by the Fz receptor and a recently

identified low-density-lipoprotein-receptor-related co-receptor, LRP6/Arrow. Overproduction

of the 200K LRP6 protein, but not of Fz, strikingly increased Dkk-1 binding as

well as the amount of the 240K cross-linked complex, which was shown to be composed

of Dkk-1 and LRP6 . Moreover, Dkk-1 function was completely independent of Fz

but LRP6 dramatically interfered with the Dkk-1 inhibition of Wnt signaling . Thus, unlike

Wnt antagonists, which exert their effects by molecular mimicry of Fz or Wnt sequestration

through other mechanisms, Dkk-1 specifically inhibits canonical Wnt signaling by

binding to the LRP6 component of the receptor complex .

S100A6 calcium binding protein is expressed in the epithelial sac of the hair follicle during

regenerative processes (Ito and Kizawa, 2001). This protein is present in the bulge

area where the stem cells are located during the catagen-telogen-anagen transition

periods .

Lu et al ., report that cytokeratin K19 is expressed in epithelial cells, basal cells of nonkeratinized

stratified squamous epithelium, epidermal cells during the embryonic stage,

and squamous carcinoma cells, but it is not expressed in adult epidermis. Interestingly,

U n d e r s t a n d i n g H a i r T r a n s p l a n t s a n d H a i r L o s s

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