Casein kinase 1-epsilon or 1-delta required for Wnt-mediated intestinal stem cell maintenance.

ABSTRACT: The intestinal epithelium holds an immense regenerative capacity mobilized by intestinal stem cells (ISCs), much of it supported by Wnt pathway activation. Several unique regulatory mechanisms ensuring optimal levels of Wnt signaling have been recognized in ISCs. Here, we identify another Wnt signaling amplifier, CKIε, which is specifically upregulated in ISCs and is essential for ISC maintenance, especially in the absence of its close isoform CKIδ. Co-ablation of CKIδ/ε in the mouse gut epithelium results in rapid ISC elimination, with subsequent growth arrest, crypt-villous shrinking, and rapid mouse death. Unexpectedly, Wnt activation is preserved in all CKIδ/ε-deficient enterocyte populations, with the exception of Lgr5⁺ ISCs, which exhibit Dvl2-dependent Wnt signaling atten

SUBMITTER: Morgenstern Y 

PROVIDER: S-EPMC5641904 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature