daf-28 encodes a C. elegans insulin superfamily member that is regulated by environmental cues and acts in the DAF-2 signaling pathway

  1. Weiqing Li,
  2. Scott G. Kennedy, and
  3. Gary Ruvkun1
  1. Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA

Abstract

In Caenorhabditis elegans, the decision to enter a developmentally arrested dauer larval stage is triggered by a combination of signals from sensory neurons in response to environmental cues, which include a dauer pheromone. These sensory inputs are coupled to the parallel DAF-2/insulin receptor-like and DAF-7/TGFβ-like signaling pathways. Although sensory inputs have been shown to physiologically regulate DAF-7/TGFβ expression, no such regulation of insulin-like ligands in the DAF-2 pathway has been reported. We show here that daf-28 encodes an insulin-like protein, which when mutated causes dauer arrest and down-regulation of DAF-2/IR signaling. A daf-28∷GFP fusion gene is expressed in ASI and ASJ, two sensory neurons that regulate dauer arrest.daf-28∷GFP expression in ASI and ASJ is down-regulated under dauer-inducing conditions and in mutants of DAF-11/guanylyl cyclase, a predicted component of the dauer-pheromone-sensing pathway. Thus,daf-28 expression in sensory neurons is regulated by the environmental cues that normally trigger dauer arrest. Among the 38C. elegans insulin genes, daf-28 is so far the only insulin mutant to affect dauer arrest. daf-28 was revealed from this functional redundancy by a dominant-negative allele that disrupts a probable proteolytic processing site required for insulin maturation. This DAF-28 mutant is likely to be poisonous to wild-type DAF-28 and other insulins.

Keywords

Footnotes

  • 1 Corresponding author.

  • E-MAIL ruvkun{at}molbio.mgh.harvard.edu; FAX (617) 726-5937.

  • Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1066503.

    • Received December 11, 2002.
    • Accepted February 10, 2003.
| Table of Contents

Life Science Alliance