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Tcf3 and Tcf4 are essential for long-term homeostasis of skin epithelia
Hoang Nguyen1,3, Bradley J Merrill1,3, Lisa Polak1, Maria Nikolova1, Michael Rendl1,3, Timothy M Shaver2, H Amalia Pasolli1 & Elaine Fuchs1
Single-layered embryonic skin either stratifies to form epidermis or responds to Wnt signaling (stabilized -catenin) to form hair follicles. Postnatally, stem cells continue to differentially use Wnt signaling in long-term tissue homeostasis. We have discovered that embryonic progenitor cells and postnatal hair follicle stem cells coexpress Tcf3 and Tcf4, which can act as transcriptional activators or repressors. Using loss-of-function studies and transcriptional analyses, we uncovered consequences to the absence of Tcf3 and Tcf4 in skin that only partially overlap with those caused by -catenin deficiency. We established roles for Tcf3 and Tcf4 in long-term maintenance and wound repair of both epidermis and hair follicles, suggesting that Tcf proteins have both Wnt-dependent and Wnt-independent roles in lineage determination.
1 Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, New York, USA.
2 Department of Molecular and Cellular Biology & Stem Cell and Regenerative Medicine Center, Baylor College of Medicine, Houston, Texas, USA.
3 Present addresses: Department of Molecular and Cellular Biology & Stem Cell and Regenerative Medicine Center, Baylor College of Medicine, Houston, Texas, USA (H.N.); Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Illinois, USA (B.J.M.); and Department of Developmental and Regenerative Biology & Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, New York, USA (M.R.).
