Cycling vrille expression is required for a functional Drosophila clock

Cell. 1999 Dec 10;99(6):661-71. doi: 10.1016/s0092-8674(00)81554-8.


We identified a novel regulatory loop within Drosophila's circadian clock. A screen for clock-controlled genes recovered vrille (vri), a transcription factor essential for embryonic development. vri is expressed in circadian pacemaker cells in larval and adult brains. vri RNA levels oscillate with a circadian rhythm. Cycling is directly regulated by the transcription factors dCLOCK and CYCLE, which are also required for oscillations of period and timeless RNA. Eliminating the normal vri cycle suppresses period and timeless expression and causes long-period behavioral rhythms and arrhythmicity, indicating that cycling vri is required for a functional Drosophila clock. We also show that dCLOCK and VRI independently regulate levels of a neuropeptide, pigment dispersing factor, which appears to regulate overt behavior.

Publication types

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

MeSH terms

  • ARNTL Transcription Factors
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Biological Clocks / genetics*
  • Brain / metabolism
  • CLOCK Proteins
  • Circadian Rhythm / genetics
  • Drosophila / embryology
  • Drosophila / genetics*
  • Drosophila / metabolism
  • Drosophila Proteins*
  • Gene Expression Regulation, Developmental
  • Insect Proteins / genetics
  • Insect Proteins / metabolism*
  • Larva
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • ARNTL Transcription Factors
  • Basic Helix-Loop-Helix Transcription Factors
  • Clk protein, Drosophila
  • Drosophila Proteins
  • Insect Proteins
  • Trans-Activators
  • Transcription Factors
  • cyc protein, Drosophila
  • vri protein, Drosophila
  • CLOCK Proteins