The researchers built mouse models for WNT10A-associated HED by deleting the particular Wnt10a gene. The mutant mice displayed the same signs and symptoms as HED patients with severe loss-of-function mutations within the WNT10A gene. Long-term absence of WNT10A leads to miniaturization associated with hair follicle structures and enlargement of the associated sweat glands, a phenomenon that is also observed in male pattern hair loss.

We showed “that β -catenin path activity and adult epithelial progenitor proliferation are decreased in the absence of WNT10A, and identify Wnt-active self-renewing come cells in affected tissues including hair follicles, sebaceous intrigue, taste buds, nails, and sweat ducts, ” the writers wrote. “ Human and mouse WNT10A mutant palmoplantar and tongue epithelia also display specific differentiation flaws that are mimicked by the loss of the transcription factor KLF4. We found that β -catenin interacts directly along with region-specific LEF/TCF [ lymphoid enhancer factor/ T-cell factor] aspects, and with KLF4 in differentiating, but not proliferating, cells to market expression of specialized keratins required for normal tissue framework and integrity. ”

Interestingly, the UPenn team also discovered that cracking and scaling of hand and foot sole skin in WNT10A patients is because of decreased expression of a structural protein called keratin nine, which is specifically expressed in these regions of skin and plays a part in its mechanical integrity.

“Our studies required us back and forth between human patients and our computer mouse model, ” said Dr . Millar. “Our goal had been to find what happened to cellular components affected by the WNT10A mutation to make better treatments. ”

Doctor Millar and her colleagues showed that decreased expansion and keratin 9 expression in the absence of WNT10A come from the failure of signaling through a well-characterized pathway that will stabilizes β -catenin, allowing it to enter the cell nucleus plus activate gene transcription. These findings indicate that small-molecule drugs that activate the β -catenin pathway downstream of WNT10A could potentially be used to treat hair thinning and hand and sole skin defects in WNT10A patients. These types of agents may also be useful for preventing hair loss in a subgroup of individuals with male-pattern baldness.