kin-19/casein kinase Ialpha has dual functions in regulating asymmetric division and terminal differentiation in C. elegans epidermal stem cells.
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Casein Kinase I (CKI) is a conserved component of the Wnt signaling pathway, which regulates cell fate determination in metazoans. We show that post-embryonic asymmetric division and fate specification of C. elegans epidermal stem cells are controlled by a non-canonical Wnt/beta-catenin signaling pathway, involving the beta-catenins WRM-1 and SYS-1, and that C. elegans kin-19/CKIalpha functions in this pathway. Furthermore, we find that kin-19 is the only member of the Wnt asymmetry pathway that functions with, or in parallel to, the heterochronic temporal patterning pathway to control withdrawal from self-renewal and subsequent terminal differentiation of epidermal stem cells. We show that, except in the case of kin-19, the Wnt asymmetry pathway and the heterochronic pathway function separately and in parallel to control different aspects of epidermal stem cell fate specification. However, given the function of kin-19/CKIalpha in both pathways, and that CKI, Wnt signaling pathway and heterochronic pathway genes are widely conserved in animals, our findings suggest that CKIalpha may function as a regulatory hub through which asymmetric division and terminal differentiation are coordinated in adult stem cells of vertebrates. (+info)
Pyrvinium, a potent small molecule Wnt inhibitor, promotes wound repair and post-MI cardiac remodeling.
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