Lipophilic regulator of a developmental switch in Caenorhabditis elegans

Matthew S. Gill, Jason M. Held, Alfred L Fisher, Bradford W. Gibson, Gordon J. Lithgow

Research output: Contribution to journalArticle

21 Citations (Scopus)

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 β(TGFPβ)-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 TGFβ 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.

Original languageEnglish (US)
Pages (from-to)413-421
Number of pages9
JournalAging Cell
Volume3
Issue number6
DOIs
StatePublished - Dec 1 2004
Externally publishedYes

Fingerprint

Caenorhabditis elegans
Hormones
Ligands
Steroid Hydroxylases
Orphan Nuclear Receptors
Phenotype
Transforming Growth Factors
Somatomedins
Cytoplasmic and Nuclear Receptors
Larva
Insulin

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Lipophilic regulator of a developmental switch in Caenorhabditis elegans. / Gill, Matthew S.; Held, Jason M.; Fisher, Alfred L; Gibson, Bradford W.; Lithgow, Gordon J.

In: Aging Cell, Vol. 3, No. 6, 01.12.2004, p. 413-421.

Research output: Contribution to journalArticle

Gill, Matthew S. ; Held, Jason M. ; Fisher, Alfred L ; Gibson, Bradford W. ; Lithgow, Gordon J. / Lipophilic regulator of a developmental switch in Caenorhabditis elegans. In: Aging Cell. 2004 ; Vol. 3, No. 6. pp. 413-421.
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