Analysis of a Caenorhabditis elegans Twist homolog identifies conserved and divergent aspects of mesodermal patterning

  1. Brian D. Harfe1,2,
  2. Ana Vaz Gomes3,
  3. Cynthia Kenyon4,
  4. Jun Liu1,
  5. Michael Krause3, and
  6. Andrew Fire1,5
  1. 1Department of Embryology, Carnegie Institution of Washington, Baltimore, Maryland 21210 USA; 2Graduate Program in Biology, The Johns Hopkins University, Baltimore, Maryland 21218 USA; 3Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, Maryland 20892-0510 USA; 4Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94143 USA

Abstract

Mesodermal development is a multistep process in which cells become increasingly specialized to form specific tissue types. InDrosophila and mammals, proper segregation and patterning of the mesoderm involves the bHLH factor Twist. We investigated the activity of a Twist-related factor, CeTwist, during Caenorhabditis elegans mesoderm development. Embryonic mesoderm in C. elegans derives from a number of distinct founder cells that are specified during the early lineages; in contrast, a single blast cell (M) is responsible for all nongonadal mesoderm formation during postembryonic development. Using immunofluorescence and reporter fusions, we determined the activity pattern of the gene encoding CeTwist. No activity was observed during specification of mesodermal lineages in the early embryo; instead, the gene was active within the M lineage and in a number of mesodermal cells with nonstriated muscle fates. A role for CeTwist in postembryonic mesodermal cell fate specification was indicated by ectopic expression and genetic interference assays. These experiments showed that CeTwist was responsible for activating two target genes normally expressed in specific subsets of nonstriated muscles derived from the M lineage. In vitro and in vivo assays suggested that CeTwist cooperates with theC. elegans E/Daughterless homolog in directly activating these targets. The two target genes that we have studied,ceh-24 and egl-15, encode an NK-2 class homeodomain and an FGF receptor (FGFR) homolog, respectively. Twist activates FGFR and NK-homeodomain target genes during mesodermal patterning ofDrosophila and similar target interactions have been proposed to modulate mesenchymal growth during closure of the vertebrate skull. These results suggest the possibility that a conserved pathway may be used for diverse functions in mesodermal specification.

Keywords

Footnotes

  • 5 Corresponding author.

  • E-MAIL fire{at}mail1.ciwemb.edu; FAX (410) 243-6311.

    • Received March 3, 1998.
    • Accepted June 17, 1998.
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