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J. Cell Biol. 158 (2): 331-344

Copyright © 2002 by the Rockefeller University Press.

Article

A developmental conundrum

a stabilized form of ß-catenin lacking the transcriptional activation domain triggers features of hair cell fate in epidermal cells and epidermal cell fate in hair follicle cells

Ramanuj DasGupta, Horace Rhee, and Elaine Fuchs

Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021

Address correspondence to Elaine Fuchs, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Ave., Box 300, New York, NY 10021. Tel.: (212) 327-7953. Fax: (212) 327-7954. E-mail: Fuchs{at}rockefeller.edu

Abstract: Wnt signaling orchestrates morphogenetic processes in which changes in gene expression are associated with dramatic changes in cell organization within developing tissue/organss. Upon signaling, excess ß-catenin not utilized at cell–cell junctions becomes stabilized, where it can provide the transcriptional activating domain for Lef/Tcf DNA binding proteins. In skin epithelium, forced stabilization of ß-catenin in epidermis promotes hair follicle morphogenesis, whereas conditional removal of ß-catenin in hair progenitor cells specifies an epidermal fate. We now report that a single protein, a stabilized version of ß-catenin lacking the COOH-terminal transactivation domain, acts in epidermis to promote hair fates and in hair cells to promote epidermal fate. This reveals fundamental differences in ways that epidermal and hair cells naturally respond to ß-catenin signaling. In exploring the phenotype, we uncovered mechanistic insights into the complexities of Lef1/Tcf/ß-catenin signaling. Importantly, how a cell will respond to the transgene product, where it will be localized, and whether it can lead to activation of endogenous ß-catenin/Tcf/Lef complexes is specifically tailored to skin stem cells, their particular lineage and their relative stage of differentiation. Finally, by varying the level of ß-catenin signaling during a cell fate program, the skin cell appears to be pliable, switching fates multiple times.

Key Words: Wnt signaling; epidermis; hair follicle; ß-catenin; morphogenesis

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