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PMID: 11445543 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skin.

Genes & development ·Vol. 15 ·No. 13 ·2001-07-01 ·Pages 1688-705

Merrill BJ, Gat U, DasGupta R, Fuchs E

Abstract

In skin, multipotent stem cells generate the keratinocytes of the epidermis, sebaceous gland, and hair follicles. In this paper, we show that Tcf3 and Lef1 control these differentiation lineages. In contrast to Lef1, which requires Wnt signaling and stabilized beta-catenin to express the hair-specific keratin genes and control hair differentiation, Tcf3 can act independently of its beta-catenin interacting domain to suppress features of epidermal terminal differentiation, in which Tcf3 is normally shut off, and promote features of the follicle outer root sheath (ORS) and multipotent stem cells (bulge), the compartments which naturally express Tcf3. These aspects of Tcf3's action are dependent on its DNA binding and Groucho repressor-binding domains. In the absence of its beta-catenin interacting domain, Lef1's behavior (Delta NLef1) seems to be markedly distinct from that of Delta NTcf3. Delta NLef1 does not suppress epidermal differentiation and promote ORS/bulge differentiation, but rather suppresses hair differentiation and gives rise to sebocyte differentiation. Taken together, these findings provide powerful evidence that the status of Tcf3/Lef complexes has a key role in controlling cell fate lineages in multipotent skin stem cells.

MeSH Terms
Animals Cell Differentiation Cell Lineage Cell Nucleus/metabolism Cells, Cultured Cytoskeletal Proteins/metabolism DNA-Binding Proteins/genetics,metabolism Epidermal Cells Epidermis/metabolism HMGB Proteins Humans Keratinocytes/cytology Lymphoid Enhancer-Binding Factor 1 Mice Mice, Transgenic Recombinant Fusion Proteins/genetics,metabolism Skin/cytology Stem Cells/cytology TCF Transcription Factors Trans-Activators Transcription Factor 7-Like 1 Protein Transcription Factors/genetics,metabolism beta Catenin
Chemicals
CTNNB1 protein, human CTNNB1 protein, mouse Cytoskeletal Proteins DNA-Binding Proteins HMGB Proteins LEF1 protein, human Lef1 protein, mouse Lymphoid Enhancer-Binding Factor 1 Recombinant Fusion Proteins TCF Transcription Factors TCF7L1 protein, human Tcf7l1 protein, mouse Trans-Activators Transcription Factor 7-Like 1 Protein Transcription Factors beta Catenin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Merrill B J
Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, Illinois 60637, USA.
Gat U
DasGupta R
Fuchs E
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.891401
Published
2001-07-01
Pages
1688-705
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC312726
Subset
IM
Grants
NIAMS NIH HHS · R01 AR031737 · United States
NIAMS NIH HHS · R01-AR31737 · United States
External Links
PubMed source DOI: 10.1101/gad.891401 PMC Full Text View journal details
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