A developmental conundrum: a stabilized form of beta-catenin lacking the transcriptional activation domain triggers features of hair cell fate in epidermal cells and epidermal cell fate in hair follicle cells.
Wnt signaling orchestrates morphogenetic processes in which changes in gene expression are associated with dramatic changes in cell organization within developing tissue/organs. Upon signaling, excess beta-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 beta-catenin in epidermis promotes hair follicle morphogenesis, whereas conditional removal of beta-catenin in hair progenitor cells specifies an epidermal fate. We now report that a single protein, a stabilized version of beta-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 beta-catenin signaling. In exploring the phenotype, we uncovered mechanistic insights into the complexities of Lef1/Tcf/beta-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 beta-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 beta-catenin signaling during a cell fate program, the skin cell appears to be pliable, switching fates multiple times.
Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Ramanuj
R
DasGupta
Horace
H
Rhee
Elaine
E
Fuchs
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002461:Cell Line, Transformed; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D006197:Hair / Q000166:cytology* / Q000502:physiology; D015603:Keratinocytes / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators; D015533:Transcriptional Activation / Q000502:physiology*; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin