title: Roles of the Wnt effector POP-1/TCF in the C. elegans endomesoderm specification gene network.
abstract: In C. elegans the 4-cell stage blastomere EMS is an endomesodermal precursor. Its anterior daughter, MS, makes primarily mesodermal cells, while its posterior daughter E generates the entire intestine. The gene regulatory network underlying specification of MS and E has been the subject of study for more than 15 years. A key component of the specification of the two cells is the involvement of the Wnt/beta-catenin asymmetry pathway, which through its nuclear effector POP-1, specifies MS and E as different from each other. Loss of pop-1 function results in the mis-specification of MS as an E-like cell, because POP-1 directly represses the end-1 and end-3 genes in MS, which would otherwise promote an endoderm fate. A long-standing question has been whether POP-1 plays a role in specifying MS fate beyond repression of endoderm fate. This question has been difficult to ask because the only chromosomal lesions that remove both end-1 and end-3 are large deletions removing hundreds of genes. Here, we report the construction of bona fide end-1 end-3 double mutants. In embryos lacking activity of end-1, end-3 and pop-1 together, we find that MS fate is partially restored, while E expresses early markers of MS fate and adopts characteristics of both MS and C. Our results suggest that POP-1 is not critical for MS specification beyond repression of endoderm specification, and reveal that Wnt-modified POP-1 and END-1/3 further reinforce E specification by repressing MS fate in E. By comparison, a previous work suggested that in the related nematode C. briggsae, Cb-POP-1 is not required to repress endoderm specification in MS, in direct contrast with Ce-POP-1, but is critical for repression of MS fate in E. The findings reported here shed new light on the flexibility of combinatorial control mechanisms in endomesoderm specification in Caenorhabditis.
authors.affiliation: Department of Biology, University of California, 2121A Genomics Building, Riverside, Riverside, CA 92521, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Owraghi
authors.forename: Gina
authors.initials: G
authors.lastname: Broitman-Maduro
authors.forename: Thomas
authors.initials: T
authors.lastname: Luu
authors.forename: Heather
authors.initials: H
authors.lastname: Roberson
authors.forename: Morris F
authors.initials: MF
authors.lastname: Maduro
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004707:Endoderm / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D017238:Genes, Helminth; D006609:High Mobility Group Proteins / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D014157:Transcription Factors / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; C096787:pop-1 protein, C elegans