January 30 2006
9:30 LSB 2320

Abstract:

Abstract
The mammalian epidermal stem cell niche serves as an ideal model system to study many facets of stem cell biology. This well defined niche (bulge) is known to maintain stem cells (SCs) in a quiescent, undifferentiated state. However, at discrete moments, these SCs divide to give rise to rapidly dividing transit amplifying progeny (TA), which will create a new hair follicle to replace that which is lost during the hair cycle. Therefore, it is essential to understand the signaling mechanisms underlying the cycle of quiescence and activation that is so unique to not only epidermal SCs but also to stem cells present in most tissues. Recently, we have shown that epidermal SCs are multipotent and microarray analysis uncovered the presence of several signaling pathways not previously shown to play a role in the epidermal stem cell niche. We showed that two of these pathways, Bmp and Fgf, play a role in SC quiescence. In addition, the Wnt pathway has long been implicated in general stem cell biology, including epidermal SCs. Despite intensive research in this area, however, very little is known about Wnt signaling in native SC niches. We have now begun to explore the impact of Wnt signaling on SC maintenance, proliferation and differentiation. By taking advantage of gain and loss of function mutants for β -catenin, we have shown that β -catenin signaling is essential for promoting the transition from quiescent SCs to proliferating transit amplifying progeny (TA). By transcriptionally profiling SCs expressing activated β -catenin, we also uncovered a discrete set of genes operating downstream of β-catenin to drive SC activation. We propose a model by which β-catenin signaling plays a role in SC identity, activation and differentiation based on the dose of its activity.