Tcf3 and Tcf4 are essential for long-term homeostasis of skin epithelia.
Single-layered embryonic skin either stratifies to form epidermis or responds to Wnt signaling (stabilized beta-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 beta-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.
Nguyen
Hoang
H
Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, New York, USA.
Merrill
Bradley J
BJ
Polak
Lisa
L
Nikolova
Maria
M
Rendl
Michael
M
Shaver
Timothy M
TM
Pasolli
H Amalia
HA
Fuchs
Elaine
E
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002454:Cell Differentiation; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006706:Homeostasis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D051820:TCF Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000073940:Transcription Factor 4; D058125:Transcription Factor 7-Like 1 Protein; D051153:Wnt Proteins / Q000378:metabolism; D014945:Wound Healing; D051176:beta Catenin / Q000172:deficiency / Q000378:metabolism
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C495267:CTNNB1 protein, mouse; D009419:Nerve Tissue Proteins; D051820:TCF Transcription Factors; C090743:Tcf4 protein, mouse; C544913:Tcf7l1 protein, mouse; D000073940:Transcription Factor 4; D058125:Transcription Factor 7-Like 1 Protein; D051153:Wnt Proteins; D051176:beta Catenin