Pharmacological approaches to nitric oxide signalling during neural development of locusts and other model insects

Abstract

A novel aspect of cellular signalling during the formation of the nervous system is the involvement of the messenger molecule nitric oxide (NO), which has been discovered in the mammalian vascular system as mediator of smooth muscle relaxation. NO is a membrane-permeant molecule, which activates soluble guanylyl cyclase (sGC) and leads to the formation of cyclic GMP (cGMP) in target cells. The analysis of specific cell types in model insects such as Locusta, Schistocerca, Acheta, Manduca, and Drosophila shows that the NO/cGMP pathway is required for the stabilization of photoreceptor growth cones at the start of synaptic assembly in the optic lobe, for regulation of cell proliferation, and for correct outgrowth of pioneer neurons. Inhibition of the NOS and sGC enzymes combined with rescue experiments show that NO, and potentially also another atypical messenger, carbon monoxide (CO), orchestrate cell migration of enteric neurons. Cultured insect embryos are accessible model systems in which the molecular pathways linking cytoskeletal rearrangement to directed cell movements can be analyzed in natural settings. Based on the results obtained from the insect models, I discuss current evidence for NO and cGMP as essential signalling molecules for the development of vertebrate brains.

Endogenous Nitric Oxide Generation Linked to Ryanodine Receptors Activates Cyclic GMP / Protein Kinase G Pathway for Cell Proliferation of Neural Stem/Progenitor Cells Derived From Embryonic Hippocampus

“…Accumulating evidence suggests that NO plays a critical role in neural development by affecting cell proliferation, migration, and differentiation (9,10). In neuronal cell lines and embryonic cells derived from neural tissues, NO attenuates cell proliferation and facilitates cell differentiation (11).…”

The Nitric Oxide-Cyclic GMP Pathway Regulates FoxO and Alters Dopaminergic Neuron Survival in Drosophila

“…cGMP is generated by the NO-mediated activation of sGCs as well as ligands-mediated activation of receptor GCs [23], [24], [25]. However, as NO generated by NOS has been implicated in PD, the role of NOS-sGC was investigated via functional assays in Drosophila .…”

Prenatal carbon monoxide impairs migration of interneurons into the cerebral cortex

“…Endogenous CO is produced by heme oxygenase (HO) via the metabolism of heme, and can signal comparably to NO via the cGMP/cGK cascade (Boehning et al, 2003). In the grasshopper embryo, enteric neurons express HO while migrating to the midgut, suggesting CO may also play a critical role in migration (Bicker, 2007). In an in vitro model Tegenge and Bicker (2009) showed that NO and cGMP positively induce neuronal migration in human neuronal precursor (NT2) cells.…”