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vrille, Pdp1, and dClock form a second feedback loop in the Drosophila circadian clock.

The Drosophila circadian clock consists of two interlocked transcriptional feedback loops. In one loop, dCLOCK/CYCLE activates period expression, and PERIOD protein then inhibits dCLOCK/CYCLE activity. dClock is also rhythmically transcribed, but its regulators are unknown. vrille (vri) and Par Domain Protein 1 (Pdp1) encode related transcription factors whose expression is directly activated by dCLOCK/CYCLE. We show here that VRI and PDP1 proteins feed back and directly regulate dClock expression. Repression of dClock by VRI is separated from activation by PDP1 since VRI levels peak 3-6 hours before PDP1. Rhythmic vri transcription is required for molecular rhythms, and here we show that the clock stops in a Pdp1 null mutant, identifying Pdp1 as an essential clock gene. Thus, VRI and PDP1, together with dClock itself, comprise a second feedback loop in the Drosophila clock that gives rhythmic expression of dClock, and probably of other genes, to generate accurate circadian rhythms.

Pubmed ID: 12581523


  • Cyran SA
  • Buchsbaum AM
  • Reddy KL
  • Lin MC
  • Glossop NR
  • Hardin PE
  • Young MW
  • Storti RV
  • Blau J



Publication Data

February 7, 2003

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM063911
  • Agency: NIGMS NIH HHS, Id: GM54339
  • Agency: NIMH NIH HHS, Id: MH61423
  • Agency: NIGMS NIH HHS, Id: R01 GM063911

Mesh Terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors
  • Behavior, Animal
  • Biological Clocks
  • CLOCK Proteins
  • Circadian Rhythm
  • Drosophila Proteins
  • Drosophila melanogaster
  • Feedback
  • Female
  • Male
  • Mutation
  • Photoreceptor Cells, Invertebrate
  • RNA, Messenger
  • Repressor Proteins
  • Transcription Factors
  • Transcriptional Activation