The DHR78 nuclear receptor is required for ecdysteroid signaling during the onset of Drosophila metamorphosis

Cell. 1998 May 15;93(4):543-55. doi: 10.1016/s0092-8674(00)81184-8.

Abstract

Pulses of ecdysteroids direct Drosophila through its life cycle by activating stage- and tissue-specific genetic regulatory hierarchies. Here we show that an orphan nuclear receptor, DHR78, functions at the top of the ecdysteroid regulatory hierarchies. Null mutations in DHR78 lead to lethality during the third larval instar with defects in ecdysteroid-triggered developmental responses. Consistent with these phenotypes, DHR78 mutants fail to activate the mid-third instar regulatory hierarchy that prepares the animal for metamorphosis. DHR78 protein is bound to many ecdysteroid-regulated puff loci, suggesting that DHR78 directly regulates puff gene expression. In addition, ectopic expression of DHR78 has no effects on development, indicating that its activity is regulated post-translationally. We propose that DHR78 is a ligand-activated receptor that plays a central role in directing the onset of Drosophila metamorphosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chromosomes / chemistry
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Drosophila / genetics
  • Drosophila / growth & development*
  • Drosophila Proteins*
  • Ecdysteroids
  • Ecdysterone / pharmacology
  • Gene Expression Regulation, Developmental / physiology
  • Genes, Insect / genetics
  • Genes, Lethal / genetics
  • Larva
  • Metamorphosis, Biological / physiology*
  • Mutation
  • Organ Specificity
  • Phenotype
  • RNA, Messenger / analysis
  • Receptors, Cytoplasmic and Nuclear / analysis
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Restriction Mapping
  • Salivary Glands / chemistry
  • Signal Transduction / physiology
  • Steroids / physiology*
  • Trachea / chemistry
  • Trachea / growth & development

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Ecdysteroids
  • Hr78 protein, Drosophila
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Steroids
  • Ecdysterone