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CLOCK:BMAL-independent circadian oscillation of zebrafish Cryptochrome1a gene

Norio Miyamura1, Jun Hirayama, Kenji Sawanobori

  • 1Department of Developmental and Regenerative Biology, Tokyo Medical and Dental University.

Biological & Pharmaceutical Bulletin
|July 3, 2009
PubMed

Insights

Zebrafish Cry1a gene circadian rhythm is independent of the CLOCK:BMAL pathway. Extracellular signal-regulated kinase (ERK) signaling influences zCry1a expression, suggesting non-canonical clock gene involvement.

Area of Science:

  • Chronobiology
  • Molecular Biology
  • Genetics

Background:

  • The vertebrate circadian clock relies on CLOCK:BMAL transcription factors regulating Cryptochrome (Cry) genes.
  • CRY proteins form a negative feedback loop by inhibiting CLOCK:BMAL-mediated transcription.
  • Zebrafish possess four Cry genes (zCry1a, 1b, 2a, 2b), all inhibiting transcription, with observed circadian expression patterns.

Purpose of the Study:

  • To investigate the CLOCK:BMAL dependency of zCry1a circadian oscillation.
  • To explore potential alternative regulatory mechanisms for zCry1a circadian expression.

Main Methods:

  • Utilized dominant-negative zCLOCK3-DeltaC to abrogate CLOCK:BMAL-dependent transcription in zebrafish cells.
  • Monitored zCry1a circadian oscillation under constant darkness.
  • Investigated the role of extracellular signal-regulated kinase (ERK) signaling pathway.

Main Results:

  • Abrogation of CLOCK:BMAL-dependent transcription did not affect zCry1a circadian oscillation.
  • Evidence suggests the ERK signaling cascade modulates zCry1a circadian expression in constant darkness.
  • zCry1a circadian oscillation is CLOCK:BMAL-independent.

Conclusions:

  • The circadian oscillation of zebrafish zCry1a is independent of the canonical CLOCK:BMAL pathway.
  • The ERK signaling cascade and potentially non-canonical clock genes contribute to zCry1a's cell-autonomous circadian expression.

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