De novo hair follicle morphogenesis and hair tumors in mice expressing a truncated β-catenin in skin

Uri Gat, Ramanuj DasGupta, Linda Degenstein, Elaine Fuchs*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

999 Scopus citations

Abstract

An effector of intercellular adhesion, β-catenin also functions in Wnt signaling, associating with Lef-1/Tcf DNA-binding proteins to form a transcription factor. We report that this pathway operates in keratinocytes and that mice expressing a stabilized β-catenin controlled by an epidermal promoter undergo a process resembling de novo hair morphogenesis. The new follicles formed sebaceous glands and dermal papilla, normally established only in embryogenesis. As in embryologically initiated hair germs, transgenic follicles induce Lef-1, but follicles are disoriented and defective in sonic hedgehog polarization. Additionally, proliferation continues unchecked, resulting in two types of tumors also found in humans. Our findings suggest that transient β-catenin stabilization may be a key player in the long- sought epidermal signal leading to hair development and implicate aberrant β-catenin activation in hair tumors.

Original languageAmerican English
Pages (from-to)605-614
Number of pages10
JournalCell
Volume95
Issue number5
DOIs
StatePublished - 25 Nov 1998
Externally publishedYes

Bibliographical note

Funding Information:
We especially thank the following: Drs. Xiantang Li and Maria Medenica (University of Chicago) for advice on pathology/diagnosis of hair tumors, Drs. Hans Clevers and Marc van de Wetering (University Hospital, Utrecht, The Netherlands) for advice and for pTOPFLASH, Dr. Cliff Tabin (Harvard Medical School, Boston, MA) for Shh cDNA, Dr. Matthew P. Scott (Stanford University, Palo Alto, CA) for Ptc cDNA, Dr. Walter Birchmeier (University of Berlin, Germany) for βcat cDNA, Dr. Cindy Loomis and Dr. Henry Sun (New York University School of Medicine, New York, NY) for AE13 and AE15 antibodies, and Dr. Rudolph Grosschedl for Lef-1 antibody. The University of Chicago Cancer Research Center supported the facilities that we used for transgenic mice generation (Alison Lawrence), DNA sequencing, and scanning electron microscopy (Dr. Edward Williams). This work was supported in part by National Institutes of Health (AR31737 and 5P50-DE11921). E. F. is an Investigator of the Howard Hughes Medical Institute. R. D-G. Is a predoctoral trainee supported by a Markey Fellowship for Molecular Medicine.

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