{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:23:46Z","timestamp":1780467826029,"version":"3.54.1"},"reference-count":92,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Council (DFG)","doi-asserted-by":"publisher","award":["Bi 262\/10-5"],"award-info":[{"award-number":["Bi 262\/10-5"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms26167783","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T07:45:31Z","timestamp":1755071131000},"page":"7783","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["CO and NO Coordinate Developmental Neuron Migration"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5957-6698","authenticated-orcid":false,"given":"Sabine","family":"Knipp","sequence":"first","affiliation":[{"name":"Core Facility Imaging, Faculty of Medicine, Johannes Kepler University Linz, 4020 Linz, Austria"},{"name":"Institute of Physiology and Cell Biology, University of Veterinary Medicine Hannover, Bischofsholer Damm 15\/102, 30125 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6617-7421","authenticated-orcid":false,"given":"Arndt","family":"Rohwedder","sequence":"additional","affiliation":[{"name":"Core Facility Imaging, Faculty of Medicine, Johannes Kepler University Linz, 4020 Linz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3158-067X","authenticated-orcid":false,"given":"Gerd","family":"Bicker","sequence":"additional","affiliation":[{"name":"Institute of Physiology and Cell Biology, University of Veterinary Medicine Hannover, Bischofsholer Damm 15\/102, 30125 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.ydbio.2012.01.012","article-title":"The enteric nervous system","volume":"366","author":"Sasselli","year":"2012","journal-title":"Dev. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.semcdb.2017.01.006","article-title":"Enteric nervous system development: A crest cell\u2019s journey from neural tube to colon","volume":"66","author":"Nagy","year":"2017","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/S0166-2236(97)01066-7","article-title":"Development of the insect stomatogastric nervous system","volume":"20","author":"Hartenstein","year":"1997","journal-title":"Trends Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1002\/dvdy.21138","article-title":"How to innervate a simple gut: Familiar themes and unique aspects in the formation of the insect enteric nervous system","volume":"236","author":"Copenhaver","year":"2007","journal-title":"Dev. Dyn."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cois.2016.08.001","article-title":"Neuronal migration during development and the amyloid precursor protein","volume":"18","author":"Copenhaver","year":"2016","journal-title":"Curr. Opin. Insect Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1002\/(SICI)1096-9861(19960902)372:4<581::AID-CNE7>3.0.CO;2-0","article-title":"Embryonic development of the enteric nervous system of the grasshopper Schistocerca americana","volume":"372","author":"Ganfornina","year":"1996","journal-title":"J. Comp. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1002\/cne.21235","article-title":"Embryonic differentiation of serotonin-containing neurons in the enteric nervous system of the locust (Locusta migratoria)","volume":"501","author":"Stern","year":"2007","journal-title":"J. Comp. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1146\/annurev-ento-013124-124333","article-title":"Phenotypic Plasticity in Locusts: Trade-Off Between Migration and Reproduction","volume":"70","author":"Guo","year":"2025","journal-title":"Annu. Rev. Entomol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1002\/dvdy.22115","article-title":"A developmental study of enteric neuron migration in the grasshopper using immunological probes","volume":"238","author":"Knipp","year":"2009","journal-title":"Dev. Dyn."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/0092-8674(87)90072-9","article-title":"Expression of fasciclin I and II glycoproteins on subsets of axon pathways during neuronal development in the grasshopper","volume":"48","author":"Bastiani","year":"1987","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3977","DOI":"10.1242\/dev.00612","article-title":"Nitric oxide and cyclic nucleotides are regulators of neuronal migration in an insect embryo","volume":"130","author":"Haase","year":"2003","journal-title":"Development"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1242\/dev.026716","article-title":"Regulation of enteric neuron migration by the gaseous messenger molecules CO and NO","volume":"136","author":"Knipp","year":"2009","journal-title":"Development"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8809","DOI":"10.1523\/JNEUROSCI.21-22-08809.2001","article-title":"Nitric Oxide Is an Essential Negative Regulator of Cell Proliferation in Xenopus Brain","volume":"21","author":"Peunova","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1146\/annurev.neuro.26.041002.131047","article-title":"Novel Neural Modulators","volume":"26","author":"Boehning","year":"2003","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1023\/B:NEUR.0000020612.87729.98","article-title":"The role of nitric oxide signaling in the formation of the neuromuscular junction","volume":"32","author":"Godfrey","year":"2003","journal-title":"J. Neurocytol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9566","DOI":"10.1073\/pnas.1633579100","article-title":"Nitric oxide negatively regulates mammalian adult neurogenesis","volume":"100","author":"Packer","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.neuron.2005.01.011","article-title":"Presynaptic and Postsynaptic Roles of NO, cGK, and RhoA in Long-Lasting Potentiation and Aggregation of Synaptic Proteins","volume":"45","author":"Wang","year":"2005","journal-title":"Neuron"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000332811","article-title":"Differential Contribution of the Guanylyl Cyclase-Cyclic GMP-Protein Kinase G Pathway to the Proliferation of Neural Stem Cells Stimulated by Nitric Oxide","volume":"21","author":"Carreira","year":"2013","journal-title":"Neurosignals"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"E4142","DOI":"10.1073\/pnas.1311927110","article-title":"Nitric oxide mediates local activity-dependent excitatory synapse development","volume":"110","author":"Nikonenko","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/bph.14532","article-title":"NO as a multimodal transmitter in the brain: Discovery and current status","volume":"176","author":"Garthwaite","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0896-6273(00)80436-5","article-title":"Nitric Oxide and Cyclic GMP Regulate Retinal Patterning in the Optic Lobe of Drosophila","volume":"20","author":"Gibbs","year":"1998","journal-title":"Neuron"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3543","DOI":"10.1242\/dev.127.16.3543","article-title":"Ecdysteroid coordinates optic lobe neurogenesis via a nitric oxide signaling pathway","volume":"127","author":"Champlin","year":"2000","journal-title":"Development"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1111\/j.1460-9568.2005.04153.x","article-title":"A role for nitric oxide in sensory-induced neurogenesis in an adult insect brain","volume":"21","author":"Cayre","year":"2005","journal-title":"Eur. J. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.cell.2015.11.047","article-title":"Nitric Oxide as a Switching Mechanism between Axon Degeneration and Regrowth during Developmental Remodeling","volume":"164","author":"Rabinovich","year":"2016","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Hou, L., Yang, P., Jiang, F., Liu, Q., Wang, X., and Kang, L. (2017). The neuropeptide F\/nitric oxide pathway is essential for shaping locomotor plasticity underlying locust phase transition. eLife, 6.","DOI":"10.7554\/eLife.22526"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Aso, Y., Ray, R.P., Long, X., Bushey, D., Cichewicz, K., Ngo, T.-T.B., Sharp, B., Christoforou, C., Hu, A., and Lemire, A.L. (2019). Nitric oxide acts as a cotransmitter in a subset of dopaminergic neurons to diversify memory dynamics. eLife, 8.","DOI":"10.7554\/eLife.49257"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Giachello, C.N.G., Fan, Y.N., Landgraf, M., and Baines, R.A. (2021). Nitric oxide mediates activity-dependent change to synaptic excitation during a critical period in Drosophila. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-99868-8"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/0304-3940(93)90673-9","article-title":"A correlation between soluble brain nitric oxide synthase and NADPH-diaphorase activity is only seen after exposure of the tissue to fixative","volume":"155","author":"Matsumoto","year":"1993","journal-title":"Neurosci. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0031-6997(24)01457-1","article-title":"Guanylyl Cyclases and Signaling by Cyclic GMP","volume":"52","author":"Lucas","year":"2000","journal-title":"Pharmacol. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7521","DOI":"10.1523\/JNEUROSCI.14-12-07521.1994","article-title":"Calcium-activated release of nitric oxide and cellular distribution of nitric oxide-synthesizing neurons in the nervous system of the locust","volume":"14","author":"Mueller","year":"1994","journal-title":"J. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1242\/jeb.198.3.821","article-title":"Nitric Oxide Synthesis in Locust Olfactory Interneurones","volume":"198","author":"Elphick","year":"1995","journal-title":"J. Exp. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/0306-4522(87)90226-0","article-title":"A new approach to immunocytochemistry of 3\u2032,5\u2032-cyclic guanosine monophosphate: Preparation, specificity, and initial application of a new antiserum against formaldehyde-fixed 3\u2032,5\u2032-cyclic guanosine monophosphate","volume":"22","author":"Vente","year":"1987","journal-title":"Neuroscience"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1126\/science.7678352","article-title":"Carbon Monoxide: A Putative Neural Messenger","volume":"259","author":"Verma","year":"1993","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0896-6273(03)00596-8","article-title":"Carbon Monoxide Neurotransmission Activated by CK2 Phosphorylation of Heme Oxygenase-2","volume":"40","author":"Boehning","year":"2003","journal-title":"Neuron"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"30927","DOI":"10.1074\/jbc.C400222200","article-title":"Heme Oxygenase-2 Is Activated by Calcium-Calmodulin","volume":"279","author":"Boehning","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1146\/annurev.pharmtox.46.120604.141053","article-title":"CO as a cellular signaling molecule","volume":"46","author":"Kim","year":"2006","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.molmed.2012.10.001","article-title":"The social network of carbon monoxide in medicine","volume":"19","author":"Wegiel","year":"2013","journal-title":"Trends Mol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lu, W., Yang, X., and Wang, B. (2022). Carbon monoxide signaling and soluble guanylyl cyclase: Facts, myths, and intriguing possibilities. Biochem. Pharmacol., 200.","DOI":"10.1016\/j.bcp.2022.115041"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/S0896-6273(00)80103-8","article-title":"Carbon Monoxide: An Endogenous Modulator of the Nitric Oxide\u2013Cyclic GMP Signaling System","volume":"16","author":"Ingi","year":"1996","journal-title":"Neuron"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1111\/j.1432-1033.2004.04077.x","article-title":"Unique features of recombinant heme oxygenase of Drosophila melanogaster compared with those of other heme oxygenases studied","volume":"271","author":"Zhang","year":"2004","journal-title":"Eur. J. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1002\/dneu.20359","article-title":"Gaseous neuromodulator-related genes expressed in the brain of honeybee Apis mellifera","volume":"67","author":"Watanabe","year":"2007","journal-title":"Dev. Neurobiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ibmb.2018.04.010","article-title":"Characterisation of Anopheles gambiae heme oxygenase and metalloporphyrin feeding suggests a potential role in reproduction","volume":"98","author":"Spencer","year":"2018","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Walter-Nuno, A.B., Taracena, M.L., Mesquita, R.D., Oliveira, P.L., and Paiva-Silva, G.O. (2018). Silencing of Iron and Heme-Related Genes Revealed a Paramount Role of Iron in the Physiology of the Hematophagous Vector Rhodnius prolixus. Front. Genet., 9.","DOI":"10.3389\/fgene.2018.00019"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5636","DOI":"10.1021\/bi00184a036","article-title":"Soluble Guanylate Cyclase from Bovine Lung: Activation with Nitric Oxide and Carbon Monoxide and Spectral Characterization of the Ferrous and Ferric States","volume":"33","author":"Stone","year":"1994","journal-title":"Biochemistry"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1111\/j.1460-9568.2004.03588.x","article-title":"An evolutionarily conserved mechanism for sensitization of soluble guanylyl cyclase reveals extensive nitric oxide-mediated upregulation of cyclic GMP in insect brain","volume":"20","author":"Ott","year":"2004","journal-title":"Eur. J. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/B978-0-12-391857-4.00009-4","article-title":"Methods for Cell and Particle Tracking","volume":"504","author":"Meijering","year":"2012","journal-title":"Methods Enzymol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/nrm2729","article-title":"Random versus directionally persistent cell migration","volume":"10","author":"Petrie","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1006\/bbrc.2000.4194","article-title":"cGMP-Dependent Protein Kinase Phosphorylates and Inactivates RhoA","volume":"280","author":"Sawada","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"41342","DOI":"10.1074\/jbc.M112.421040","article-title":"Direct Binding and Regulation of RhoA Protein by Cyclic GMP-dependent Protein Kinase I\u03b1","volume":"287","author":"Kato","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ceb.2015.08.005","article-title":"Rho GTPase signalling in cell migration","volume":"36","author":"Ridley","year":"2015","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1126\/science.279.5350.509","article-title":"Rho GTPases and the Actin Cytoskeleton","volume":"279","author":"Hall","year":"1998","journal-title":"Science"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1006\/dbio.1998.9066","article-title":"A Delayed Role for Nitric Oxide-Sensitive Guanylate Cyclases in a Migratory Population of Embryonic Neurons","volume":"204","author":"Wright","year":"1998","journal-title":"Dev. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1126\/science.1470903","article-title":"The Molecule of the Year","volume":"258","author":"Koshland","year":"1992","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"re6","DOI":"10.1126\/stke.2302004re6","article-title":"Carbon Monoxide: To Boldly Go Where NO Has Gone Before","volume":"2004","author":"Ryter","year":"2004","journal-title":"Sci. STKE"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/S0896-6273(00)80310-4","article-title":"(S)NO Signals: Translocation, Regulation, and a Consensus Motif","volume":"18","author":"Stamler","year":"1997","journal-title":"Neuron"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1007\/s000180050354","article-title":"S-Nitrosylation of proteins","volume":"55","author":"Broillet","year":"1999","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"19777","DOI":"10.1073\/pnas.0605907103","article-title":"Nitric oxide synthase generates nitric oxide locally to regulate compartmentalized protein S-nitrosylation and protein trafficking","volume":"103","author":"Iwakiri","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1021\/acschemneuro.8b00187","article-title":"cAMP, Ca2+, pHi, and NO Regulate H-like Cation Channels That Underlie Feeding and Locomotion in the Predatory Sea Slug Pleurobranchaea californica","volume":"9","author":"Green","year":"2018","journal-title":"ACS Chem. Neurosci."},{"key":"ref_59","first-page":"37","article-title":"Carbon monoxide: A critical quantitative analysis and review of the extent and limitations of its second messenger function","volume":"37","author":"Levitt","year":"2015","journal-title":"Clin. Pharmacol. Adv. Appl."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1126\/science.1105010","article-title":"Hemoxygenase-2 Is an Oxygen Sensor for a Calcium-Sensitive Potassium Channel","volume":"306","author":"Williams","year":"2004","journal-title":"Science"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.resp.2012.04.004","article-title":"Evolutionary and comparative aspects of nitric oxide, carbon monoxide and hydrogen sulfide","volume":"184","author":"Olson","year":"2012","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/nrd3228","article-title":"The therapeutic potential of carbon monoxide","volume":"9","author":"Motterlini","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Maccallini, C., Budriesi, R., De Filippis, B., and Amoroso, R. (2024). Advancements in the Research of New Modulators of Nitric Oxide Synthases Activity. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25158486"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1126\/science.271.5251.978","article-title":"Chain Migration of Neuronal Precursors","volume":"271","author":"Lois","year":"1996","journal-title":"Science"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/S0896-6273(00)80317-7","article-title":"Direct Evidence for Homotypic, Glia-Independent Neuronal Migration","volume":"18","author":"Wichterle","year":"1997","journal-title":"Neuron"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1111\/j.1460-9568.2007.05672.x","article-title":"Migrating neuroblasts of the rostral migratory stream are putative targets for the action of nitric oxide","volume":"26","author":"Crespo","year":"2007","journal-title":"Eur. J. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1096\/fj.02-0359fje","article-title":"Visualization of gaseous monoxide reception by soluble guanylate cyclase in the rat retina","volume":"17","author":"Kajimura","year":"2003","journal-title":"FASEB J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.neuroscience.2015.10.056","article-title":"Regulation of electrical activity and neuronal excitability in Helisoma trivolvis by carbon monoxide","volume":"311","author":"Estes","year":"2015","journal-title":"Neuroscience"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1002\/dneu.22430","article-title":"Modulation of growth cone filopodial length by carbon monoxide","volume":"77","author":"Estes","year":"2016","journal-title":"Dev. Neurobiol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Guan, G., Cannon, R.D., Coates, D.E., and Mei, L. (2023). Effect of the Rho-Kinase\/ROCK Signaling Pathway on Cytoskeleton Components. Genes, 14.","DOI":"10.3390\/genes14020272"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1042\/EBC20190015","article-title":"Actin dynamics in cell migration","volume":"63","author":"Schaks","year":"2019","journal-title":"Essays Biochem."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"van Haastert, P.J.M., Keizer-Gunnink, I., Pots, H., Ortiz-Mateos, C., Veltman, D., van Egmond, W., and Kortholt, A. (2021). Forty-five years of cGMP research in Dictyostelium: Understanding the regulation and function of the cGMP pathway for cell movement and chemotaxis. Mol. Biol. Cell, 32.","DOI":"10.1091\/mbc.E21-04-0171"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"16897","DOI":"10.1523\/JNEUROSCI.1871-13.2013","article-title":"Soluble Guanylate Cyclase Generation of cGMP Regulates Migration of MGE Neurons","volume":"33","author":"Mandal","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"14515","DOI":"10.1073\/pnas.0505136102","article-title":"Imaging the nanomolar range of nitric oxide with an amplifier-coupled fluorescent indicator in living cells","volume":"102","author":"Sato","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"22060","DOI":"10.1073\/pnas.1013147107","article-title":"Exquisite sensitivity to subsecond, picomolar nitric oxide transients conferred on cells by guanylyl cyclase-coupled receptors","volume":"107","author":"Batchelor","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.niox.2017.09.001","article-title":"Real-time visualization of distinct nitric oxide generation of nitric oxide synthase isoforms in single cells","volume":"70","author":"Eroglu","year":"2017","journal-title":"Nitric Oxide"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"9790","DOI":"10.1002\/ange.201203684","article-title":"A Selective Fluorescent Probe for Carbon Monoxide Imaging in Living Cells","volume":"124","author":"Wang","year":"2012","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1002\/cne.903500304","article-title":"Embryonic development of the stomatogastric nervous system in Drosophila","volume":"350","author":"Hartenstein","year":"1994","journal-title":"J. Comp. Neurol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ibmb.2015.07.003","article-title":"From mouth to anus: Functional and structural relevance of enteric neurons in the Drosophila melanogaster gut","volume":"67","author":"Kuraishi","year":"2015","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4541","DOI":"10.1242\/dev.127.21.4541","article-title":"Nitric oxide and cGMP influence axonogenesis of antennal pioneer neurons","volume":"127","author":"Seidel","year":"2000","journal-title":"Development"},{"key":"ref_81","first-page":"643","article-title":"An intact insect embryo for developmental neurotoxicity testing of directed axonal elongation","volume":"36","author":"Bergmann","year":"2019","journal-title":"ALTEX"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4099","DOI":"10.1007\/s00204-020-02929-6","article-title":"A locust embryo as predictive developmental neurotoxicity testing system for pioneer axon pathway formation","volume":"94","author":"Bode","year":"2020","journal-title":"Arch. Toxicol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Bode, K., Nolte, L., Kamin, H., Desens, M., Ulmann, A., Bergmann, G.A., Betker, P., Reitmeier, J., Ripken, T., and Stern, M. (2020). Scanning laser optical tomography resolves developmental neurotoxic effects on pioneer neurons. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-59562-7"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Bergmann, G.A., and Bicker, G. (2021). Cholinergic calcium responses in cultured antennal lobe neurons of the migratory locust. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-89374-2"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1242\/dev.54.1.47","article-title":"Quantitative staging of embryonic development of the grasshopper, Schistocerca nitens","volume":"54","author":"Bentley","year":"1979","journal-title":"Development"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/(SICI)1096-9861(19980427)394:1<1::AID-CNE1>3.0.CO;2-4","article-title":"Developing Grasshopper Neurons Show Variable Levels of Guanylyl Cyclase Activity on Arrival at Their Targets","volume":"394","author":"Ball","year":"1998","journal-title":"J. Comp. Neurol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.21105\/joss.01686","article-title":"Welcome to the Tidyverse","volume":"4","author":"Wickham","year":"2019","journal-title":"J. Open Source Softw."},{"key":"ref_90","unstructured":"Kassambara, A. (2025, March 15). rstatix: Pipe-Friendly Framework for Basic Statistical Tests. R Package Version 0.7.2. Available online: https:\/\/rpkgs.datanovia.com\/rstatix\/."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1080\/00949655.2010.520163","article-title":"Comparisons of various types of normality tests","volume":"81","author":"Yap","year":"2011","journal-title":"J. Stat. Comput. Sim."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Diedenhofen, B., and Musch, J. (2015). cocor: A Comprehensive Solution for the Statistical Comparison of Correlations. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0121945"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/16\/7783\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:25:37Z","timestamp":1760034337000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/16\/7783"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,12]]},"references-count":92,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ijms26167783"],"URL":"https:\/\/doi.org\/10.3390\/ijms26167783","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,12]]}}}