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Wnt signaling, asymmetric divisions and generation of a stem cell niche
Author(s) -
Kimble Judith,
Kidd Ambrose R.,
Lam Ngan,
Chesney Michael A.,
Phillips Bryan T.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a456-b
Subject(s) - wnt signaling pathway , biology , transcription factor , cell fate determination , microbiology and biotechnology , beta catenin , lrp5 , lrp6 , ectopic expression , genetics , gene , nuclear localization sequence , signal transduction
Wnt signaling typically activates the transcription of target genes by means of a TCF/LEF transcription factor and a β‐catenin coactivator. We have focused on Wnt signaling in C. elegans and its regulation of an asymmetric division that generates a stem cell niche. The nematode Wnt control of asymmetric divisions appears unusual: the daughter dependent on Wnt signaling has less nuclear POP‐1/TCF than its sister, which adopts a fate independent of Wnt signaling. One explanation has been that the decrease in nuclear POP‐1/TCF de‐represses transcription of Wnt‐dependent target genes. Recently we identified SYS‐1, a novel protein by amino acid sequence that functions as a transcriptional co‐activator with POP‐1; several lines of evidence suggest that SYS‐1 is in fact a functional β‐catenin. Complementary approaches support the idea that Wnt signaling controls the ratio of POP‐1/TCF to SYS‐1/β‐catenin to achieve transcriptional activation. These approaches include tissue culture reporter assays, null mutants and genetic interactions, ectopic SYS‐1 expression, and identification of a target gene controlled directly by POP‐1/TCF and SYS‐1/β‐catenin. We suggest that Wnt signaling can activate target genes either by increasing the level of nuclear SYS‐1/β‐catenin (the canonical pathway) or by lowering the level of nuclear POP‐1/TCF (nematode pathway). The Wnt‐dependent target gene that we have identified encodes a homeodomain transcription factor that is both necessary and sufficient for specification of the niche fate.