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Lipophilic regulator of a developmental switch in Caenorhabditis elegans

Academic Article
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Overview

authors

  • Gill, Matt
  • Held, J. M.
  • Fisher, A. L.
  • Gibson, B. W.
  • Lithgow, G. J.

publication date

  • December 2004

journal

  • Aging Cell  Journal

abstract

  • Abstract In Caenorhabditis elegans, the decision to develop into a reproductive adult or arrest as a dauer larva is influenced by multiple pathways including insulin-like and transforming growth factor beta (TGFbeta)-like signalling pathways. It has been proposed that lipophilic hormones act downstream of these pathways to regulate dauer formation. One likely target for such a hormone is DAF-12, an orphan nuclear hormone receptor that mediates these developmental decisions and also influences adult lifespan. In order to find lipophilic hormones we have generated lipophilic extracts from mass cultures of C. elegans and shown that they rescue the dauer constitutive phenotype of class 1 daf-2 insulin signalling mutants and the TGFbeta signalling mutant daf-7. These extracts are also able to rescue the lethal dauer phenotype of daf-9 mutants, which lack a P450 steroid hydroxylase thought to be involved in the synthesis of the DAF-12 ligand; extracts, however, have no effect on a DAF-12 ligand binding domain mutant that is predicted to be ligand insensitive. The production of this hormone appears to be DAF-9 dependent as extracts from a daf-9;daf-12 double mutant do not exhibit this activity. Preliminary fractionation of the lipophilic extracts shows that the activity is hydrophobic with some polar properties, consistent with a small lipophilic hormone. We propose that the dauer rescuing activity is a hormone synthesized by DAF-9 that acts through DAF-12.

subject areas

  • Alleles
  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Cytochrome P-450 Enzyme System
  • Insulin
  • Larva
  • Ligands
  • Mutation
  • Phenotype
  • Receptors, Cytoplasmic and Nuclear
  • Signal Transduction
  • Transforming Growth Factor beta
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Identity

International Standard Serial Number (ISSN)

  • 1474-9718

Digital Object Identifier (DOI)

  • 10.1111/j.1474-9728.2004.00126.x

PubMed ID

  • 15569358
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Additional Document Info

start page

  • 413

end page

  • 421

volume

  • 3

issue

  • 6

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