kin-19/casein kinase Iα has dual functions in regulating asymmetric division and terminal differentiation in C. elegans epidermal stem cells

Cell Cycle. 2010 Dec 1;9(23):4748-65. doi: 10.4161/cc.9.23.14092. Epub 2010 Dec 1.

Abstract

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/β-catenin signaling pathway, involving the β-catenins WRM-1 and SYS-1, and that C. elegans kin-19/CKIα 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/CKIα in both pathways, and that CKI, Wnt signaling pathway and heterochronic pathway genes are widely conserved in animals, our findings suggest that CKIα may function as a regulatory hub through which asymmetric division and terminal differentiation are coordinated in adult stem cells of vertebrates.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / enzymology*
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Caenorhabditis elegans Proteins / physiology*
  • Casein Kinase Ialpha / metabolism
  • Casein Kinase Ialpha / physiology*
  • Cell Differentiation
  • Cell Division
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Epidermal Cells
  • Gene Knockdown Techniques
  • Larva / enzymology
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Protein Kinases / physiology*
  • RNA Interference
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / enzymology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Wnt Proteins / metabolism
  • beta Catenin / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Cytoskeletal Proteins
  • Sys-1 protein, C elegans
  • Transcription Factors
  • WRM-1 protein, C elegans
  • Wnt Proteins
  • beta Catenin
  • Protein Kinases
  • Casein Kinase Ialpha
  • KIN-19 protein, C elegans