CO and NO Coordinate Developmental Neuron Migration

Similarly to the short-lived messenger nitric oxide (NO), the more stable carbon monoxide (CO) molecule can also activate soluble guanylyl cyclase (sGC) to increase cGMP levels. However, CO-induced cGMP production is much less efficient. Using an accessible invertebrate model, we dissect a potential interaction between the canonical NO/sGC/cGMP and CO signalling pathways during development. The embryonic midgut of locusts is innervated by neurons that migrate in four discrete chains on its outer surface. Transcellular diffusing NO stimulates enteric neuron migration via cGMP signalling. The application of an NO donor results in virtually all enteric neurons being cGMP-immunoreactive while CO increases cGMP production only in approximately 33% of the migrating neurons. Cellular CO release appears to act as a slow down signal for motility. We quantify how CO specifically increases the interneuronal distance during chain migration. Moreover, time-lapse microscopy shows that CO reduces the directionality of the migrating neurons. These findings support the function of NO and CO as antagonistic signals for the coordination of collective cell migration during the development of the enteric nervous system. These experiments and the resulting insights into basic scientific questions prove once more that locust embryos are not only preparations for basic research, but also relevant models for screening of drugs targeting NO and CO signalling pathways as well as for isolating compounds affecting neuronal motility in general.