Dynamics of a Developmental Switch: Recursive Intracellular and Intranuclear Redistribution of Caenorhabditis Elegans POP-1 Parallels Wnt-inhibited Transcriptional Repression

Dev Biol. 2002 Aug 1;248(1):128-42. doi: 10.1006/dbio.2002.0721.

Abstract

POP-1, a Tcf/Lef factor, functions throughout Caenorhabditis elegans development as a Wnt-dependent reiterative switch to generate nonequivalent sister cells that are born by anterior-posterior cell divisions. We have observed the interaction between POP-1 and a target gene that it represses as it responds to Wnt signaling. Dynamic observations in living embryos reveal that POP-1 undergoes Wnt-dependent nucleocytoplasmic redistribution immediately following cytokinesis, explaining the differential nuclear POP-1 levels in nonequivalent sister cells. In unsignaled (anterior) but not Wnt-signaled (posterior) sister cells, POP-1 progressively coalesces into subnuclear domains during interphase, coincident with its action as a repressor. While the asymmetric distribution of POP-1 in nonequivalent sisters apparently requires a 124-amino-acid internal domain, neither the HMG box nor beta-catenin interaction domains are required. We find that a transcriptional activator, MED-1, associates in vivo with the end-1 and end-3 target genes in the mesoderm (anterior sister) and in the endoderm (posterior sister) following the asymmetric cell division that subdivides the mesendoderm. However, in the anterior sister, binding of POP-1 to the end-1 and end-3 genes blocks their expression. In vivo, binding of POP-1 to the end-1 and end-3 targets (in the posterior sister) is blocked by Wnt/MAPK signaling. Thus, a Tcf/Lef factor represses transactivation of genes in an unsignaled daughter cell by abrogating the function of a bound activator.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins*
  • Cell Division
  • Cell Nucleus / metabolism
  • Chromosomes / metabolism
  • Cloning, Molecular
  • Cytoplasm / metabolism
  • Cytoskeletal Proteins / metabolism
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Developmental*
  • High Mobility Group Proteins / biosynthesis*
  • High Mobility Group Proteins / genetics*
  • Immunohistochemistry
  • In Situ Hybridization
  • Lymphoid Enhancer-Binding Factor 1
  • MAP Kinase Signaling System
  • Microscopy, Fluorescence
  • Models, Biological
  • Models, Genetic
  • Mutation
  • Plasmids / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins / metabolism*
  • Signal Transduction
  • Time Factors
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • Transcriptional Activation
  • Transgenes
  • Wnt Proteins
  • Zebrafish Proteins*
  • beta Catenin

Substances

  • Caenorhabditis elegans Proteins
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Lymphoid Enhancer-Binding Factor 1
  • Proto-Oncogene Proteins
  • Trans-Activators
  • Transcription Factors
  • Wnt Proteins
  • Zebrafish Proteins
  • beta Catenin
  • pop-1 protein, C elegans