title: Nitric oxide and cyclic nucleotides are regulators of neuronal migration in an insect embryo.
abstract: The dynamic regulation of nitric oxide synthase (NOS) activity and cGMP levels suggests a functional role in the development of nervous systems. We report evidence for a key role of the NO/cGMP signalling cascade on migration of postmitotic neurons in the enteric nervous system of the embryonic grasshopper. During embryonic development, a population of enteric neurons migrates several hundred micrometers on the surface of the midgut. These midgut neurons (MG neurons) exhibit nitric oxide-induced cGMP-immunoreactivity coinciding with the migratory phase. Using a histochemical marker for NOS, we identified potential sources of NO in subsets of the midgut cells below the migrating MG neurons. Pharmacological inhibition of endogenous NOS, soluble guanylyl cyclase (sGC) and protein kinase G (PKG) activity in whole embryo culture significantly blocks MG neuron migration. This pharmacological inhibition can be rescued by supplementing with protoporphyrin IX free acid, an activator of sGC, and membrane-permeant cGMP, indicating that NO/cGMP signalling is essential for MG neuron migration. Conversely, the stimulation of the cAMP/protein kinase A signalling cascade results in an inhibition of cell migration. Activation of either the cGMP or the cAMP cascade influences the cellular distribution of F-actin in neuronal somata in a complementary fashion. The cytochemical stainings and experimental manipulations of cyclic nucleotide levels provide clear evidence that NO/cGMP/PKG signalling is permissive for MG neuron migration, whereas the cAMP/PKA cascade may be a negative regulator. These findings reveal an accessible invertebrate model in which the role of the NO and cyclic nucleotide signalling in neuronal migration can be analyzed in a natural setting.
authors.affiliation: School of Veterinary Medicine Hannover, Cell Biology, Bischofsholer Damm 15, D-30173 Hannover, Germany.
authors.forename: Annely
authors.initials: A
authors.lastname: Haase
authors.forename: Gerd
authors.initials: G
authors.lastname: Bicker
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004064:Digestive System / Q000196:embryology; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009712:Nucleotides, Cyclic / Q000378:metabolism*; D009987:Orthoptera / Q000196:embryology*
chemical_list: D000199:Actins; D009712:Nucleotides, Cyclic; D009569:Nitric Oxide; D000242:Cyclic AMP; D009252:NADPH Dehydrogenase; D006152:Cyclic GMP