Both insulin and calcium channel signaling are required for developmental regulation of serotonin synthesis in the chemosensory ADF neurons of Caenorhabditis elegans.
Proper calcium channel and insulin signaling are essential for normal brain development. Leaner mice with a mutation in the P/Q-type voltage-gated calcium channel, Cacna1a, develop cerebellar atrophy and mutations in the homologous human gene are associated with increased migraine and seizure tendency. Similarly, abnormalities in insulin signaling are associated with abnormal brain growth and migraine tendency. Previously, we have shown that in the ADF chemosensory neurons of Caenorhabditis elegans UNC-2/Ca(2+) channel function affects TGF-beta-dependent developmental regulation of tryptophan hydroxylase, the rate-limiting enzyme in serotonin synthesis. Here we show that developmental expression of a tryptophan hydroxylase: :GFP reporter construct is similarly decreased by reduction-of-function mutations in the daf-2/insulin receptor. This decreased expression of tryptophan hydroxylase observed in both the daf-2 and unc-2 mutant backgrounds is suppressible either genetically by reduction-of-function mutations in the daf-16/forkhead transcription factor, an effector of the DAF-2/insulin receptor, or pharmacologically by the serotonin receptor antagonist cyproheptadine. Overall, these data suggest that both UNC-2 and DAF-2 function are required in the developmental regulation of DAF-16 and serotonin-dependent inhibition of tryptophan hydroxylase expression.
Estevez
Annette O
AO
Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
Cowie
Robin H
RH
Gardner
Kathy L
KL
Estevez
Miguel
M
D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling; D018507:Gene Expression Regulation, Developmental; D007328:Insulin / Q000378:metabolism*; D007814:Larva / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D012701:Serotonin / Q000096:biosynthesis*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology; D014365:Tryptophan Hydroxylase / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D015220:Calcium Channels; D007328:Insulin; D016212:Transforming Growth Factor beta; D012701:Serotonin; D014365:Tryptophan Hydroxylase