title: Specific roles for the GATA transcription factors end-1 and end-3 during C. elegans E-lineage development.
abstract: end-1 and end-3 are GATA transcription factors important for specifying endoderm cell fate in Caenorhabditis elegans. Deletion of both factors together results in larval arrest, 0% survival and a fate change in the endoderm-specifying E lineage. Individual deletions of either factor, however, result in the development of viable, fertile adults, with 100% of worms developing to adults for end-1(-) and 95% for end-3(-). We sought to quantify the variable phenotypes seen in both deletions using automated cell lineaging. We quantified defects in cell lifetime, cell movement and division axis in end-3(-) embryos, while quantifying perturbations in downstream reporter gene expression in strains with homozygous deletions for either gene, showing that each deletion leads to a unique profile of downstream perturbations in gene expression and cellular phenotypes with a high correlation between early and late defects. Combining observations in both cellular and gene expression defects we found that misaligned divisions at the E2 stage resulted in ectopic expression of the Notch target ref-1 in end-3(-) embryos. Using a maximum likelihood phylogenetic approach we found end-1 and end-3 split to form two distinct clades within the Caenorhabditis lineage with distinct DNA-binding structures. These results indicate that end-1 and end-3 have each evolved into genes with unique functions during endoderm development, that end-3(-) embryos have a delay in the onset of E lineage cell fate and that end-1 has only a partially penetrant ability to activate E lineage fate.
authors.affiliation: Department of Genome Sciences, University of Washington School of Medicine, 1705 NE Pacific Street, Seattle, WA 98195, USA. maxboeck@u.washington.edu
authors.forename: Max E
authors.initials: ME
authors.lastname: Boeck
authors.forename: Tom
authors.initials: T
authors.lastname: Boyle
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Bao
authors.forename: John
authors.initials: J
authors.lastname: Murray
authors.forename: Barbara
authors.initials: B
authors.lastname: Mericle
authors.forename: Robert
authors.initials: R
authors.lastname: Waterston
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology; D002465:Cell Movement; D017124:Conserved Sequence; D004707:Endoderm / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D019143:Evolution, Molecular; D050980:GATA Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D017238:Genes, Helminth; D017930:Genes, Reporter; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D029742:Caenorhabditis elegans Proteins; D050980:GATA Transcription Factors; D014157:Transcription Factors; C109211:END-1 protein, C elegans; C504457:END-3 protein, C elegans; C428453:ref-1 protein, C elegans