A screen for secreted factors of the suprachiasmatic nucleus

Methods Enzymol. 2005;393:645-63. doi: 10.1016/S0076-6879(05)93034-6.


The circadian clock in the suprachiasmatic nucleus (SCN) drives daily locomotor activity rhythms presumably by secreting diffusible factors whose target sites are accessible from the third ventricle of the hypothalamus. This article describes the methodology of a systematic molecular and behavioral screen to identify "locomotor factors" of the SCN. To find SCN-secreted factors not previously documented, a hamster SCN cDNA library was screened in a yeast signal sequence trap. In a subsequent behavioral screen, newly identified and previously documented SCN factors were tested for an effect on locomotor activity rhythms by chronic infusion into the third ventricle of hamsters. Using this approach combined with further experiments, we identified transforming growth factor-alpha (TGF-alpha) as a likely SCN inhibitor of locomotion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Biological Clocks / drug effects
  • Circadian Rhythm / drug effects
  • Cricetinae
  • DNA, Complementary / isolation & purification
  • Drug Evaluation, Preclinical / methods
  • Genetic Techniques
  • Genetic Vectors
  • Injections, Intraventricular
  • Male
  • Mesocricetus
  • Motor Activity / drug effects
  • Peptide Library
  • Protein Sorting Signals / genetics
  • Saccharomyces cerevisiae / genetics
  • Suprachiasmatic Nucleus / metabolism*
  • Transforming Growth Factor alpha / metabolism


  • DNA, Complementary
  • Peptide Library
  • Protein Sorting Signals
  • Transforming Growth Factor alpha