title: Regulation of enteric neuron migration by the gaseous messenger molecules CO and NO.
abstract: The enteric nervous system (ENS) of insects is a useful model to study cell motility. Using small-molecule compounds to activate or inactivate biosynthetic enzymes, we demonstrate that the gaseous messenger molecules carbon monoxide (CO) and nitric oxide (NO) regulate neuron migration in the locust ENS. CO is produced by heme oxygenase (HO) enzymes and has the potential to signal via the sGC/cGMP pathway. While migrating on the midgut, the enteric neurons express immunoreactivity for HO. Here, we show that inhibition of HO by metalloporphyrins promotes enteric neuron migration in intact locust embryos. Thus, the blocking of enzyme activity results in a gain of function. The suppression of migratory behavior by activation of HO or application of a CO donor strongly implicates the release of CO as an inhibitory signal for neuron migration in vivo. Conversely, inhibition of nitric oxide synthase or application of the extracellular gaseous molecule scavenger hemoglobin reduces cell migration. The cellular distribution of NO and CO biosynthetic enzymes, together with the results of the chemical manipulations in whole embryo culture suggest CO as a modulator of transcellular NO signals during neuronal migration. Thus, we provide the first evidence that CO regulates embryonic nervous system development in a rather simple invertebrate model.
authors.affiliation: University of Veterinary Medicine Hannover, Division of Cell Biology, Institute of Physiology, Bischofsholer Damm 15, D-30173 Hannover, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Knipp
authors.forename: Gerd
authors.initials: G
authors.lastname: Bicker
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002248:Carbon Monoxide / Q000378:metabolism*; D002384:Catalysis; D002465:Cell Movement; D006152:Cyclic GMP / Q000378:metabolism; D004064:Digestive System / Q000166:cytology / Q000196:embryology / Q000201:enzymology; D017615:Enteric Nervous System / Q000166:cytology* / Q000196:embryology / Q000201:enzymology; D006110:Grasshoppers / Q000166:cytology*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D009569:Nitric Oxide; D002248:Carbon Monoxide; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing); D006152:Cyclic GMP