Transient activation of beta -catenin signaling in cutaneous keratinocytes is sufficient to trigger the active growth phase of the hair cycle in mice.

Wnts have key roles in many developmental processes, including hair follicle growth and differentiation. Stabilization of beta-catenin is essential in the canonical Wnt signaling pathway. We developed transgenic mice expressing a regulated form of beta-catenin in the skin. Chronic activation of beta-catenin in resting (telogen) hair follicles resulted in changes consistent with induction of an exaggerated, aberrant growth phase (anagen). Transient activation of beta-catenin produced a normal anagen. Our data lend strong support to the notion that a Wnt/beta-catenin signal operating on hair follicle precursor cells serves as a crucial proximal signal for the telogen-anagen transition.

[1]  R. Paus,et al.  What controls hair follicle cycling? , 1999, Experimental dermatology.

[2]  M. Peifer,et al.  Wnt signaling in oncogenesis and embryogenesis--a look outside the nucleus. , 2000, Science.

[3]  M. Vidal,et al.  Sequences 5' of the bovine keratin 5 gene direct tissue- and cell-type-specific expression of a lacZ gene in the adult and during development. , 1994, Differentiation; research in biological diversity.

[4]  C. Dang,et al.  Neoplastic Transformation of RK3E by Mutant β-Catenin Requires Deregulation of Tcf/Lef Transcription but Not Activation of c-myc Expression , 1999, Molecular and Cellular Biology.

[5]  Kathleen R. Cho,et al.  ITF-2, a downstream target of the Wnt/TCF pathway, is activated in human cancers with beta-catenin defects and promotes neoplastic transformation. , 2002, Cancer cell.

[6]  S. Millar,et al.  Molecular mechanisms regulating hair follicle development. , 2002, The Journal of investigative dermatology.

[7]  W. Birchmeier,et al.  β-Catenin Controls Hair Follicle Morphogenesis and Stem Cell Differentiation in the Skin , 2001, Cell.

[8]  E. Fuchs,et al.  At the roots of a never-ending cycle. , 2001, Developmental cell.

[9]  R. Smart,et al.  17β-Estradiol and ICI-182780 regulate the hair follicle cycle in mice through an estrogen receptor-α pathway , 2000 .

[10]  Sarah E. Millar,et al.  Characterization of Wnt gene expression in developing and postnatal hair follicles and identification of Wnt5a as a target of Sonic hedgehog in hair follicle morphogenesis , 2001, Mechanisms of Development.

[11]  G. Evan,et al.  A modified oestrogen receptor ligand-binding domain as an improved switch for the regulation of heterologous proteins. , 1995, Nucleic acids research.

[12]  E. Fuchs,et al.  De Novo Hair Follicle Morphogenesis and Hair Tumors in Mice Expressing a Truncated β-Catenin in Skin , 1998, Cell.

[13]  P. Polakis.  Wnt signaling and cancer. , 2000, Genes & development.

[14]  E. Fuchs,et al.  Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation. , 1999, Development.

[15]  S. Millar,et al.  WNT signals are required for the initiation of hair follicle development. , 2002, Developmental cell.

[16]  I Fariñas,et al.  Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1-deficient mice. , 1994, Genes & development.

[17]  E. Fuchs,et al.  Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skin. , 2001, Genes & development.

[18]  R Paus,et al.  A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages. , 2001, The Journal of investigative dermatology.

[19]  R. Burgeson,et al.  Wnt signaling maintains the hair-inducing activity of the dermal papilla. , 2000, Genes & development.

[20]  R. Smart,et al.  An estrogen receptor pathway regulates the telogen-anagen hair follicle transition and influences epidermal cell proliferation. , 1996, Proceedings of the National Academy of Sciences of the United States of America.