Dynamics of a developmental switch: recursive intracellular and intranuclear redistribution of Caenorhabditis elegans POP-1 parallels Wnt-inhibited transcriptional repression.
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.
Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA.
Morris F
MF
Maduro
Rueyling
R
Lin
Joel H
JH
Rothman
D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D002875:Chromosomes / Q000378:metabolism; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006609:High Mobility Group Proteins / Q000096:biosynthesis* / Q000235:genetics*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051821:Lymphoid Enhancer-Binding Factor 1; D020935:MAP Kinase Signaling System; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008957:Models, Genetic; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D019076:Transgenes; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; C096787:pop-1 protein, C elegans