{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:57:46Z","timestamp":1790254666346,"version":"4.1.0"},"reference-count":53,"publisher":"The Company of Biologists","issue":"20","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,10,15]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>Helisoma trivolvis embryos display a cilia-driven rotational behavior that is regulated by a pair of serotonergic neurons named ENC1s. As these cilio-excitatory motor neurons contain an apical dendrite ending in a chemosensory dendritic knob at the embryonic surface, they probably function as sensorimotor neurons. Given that nitric oxide (NO) is often associated with sensory neurons in invertebrates, and has also been implicated in the control of ciliary activity, we examined the expression of NO synthase (NOS) activity and possible function of NO in regulating the rotational behavior in H. trivolvis embryos. NADPH diaphorase histochemistry on stage E25-E30 embryos revealed NOS expression in the protonephridia, buccal mass,dorsolateral ciliary cells and the sensory dendritic knobs of ENC1. At stages E35-40, the pedal ciliary cells and ENC1's soma, apical dendrite and proximal descending axon were also stained. In stage E25 embryos, optimal doses of the NO donors SNAP and SNP increased the rate of embryonic rotation by twofold, in contrast to the fourfold increase caused by 100 \u03bcmol l-1serotonin. The NOS inhibitors L-NAME (10 mmol l-1) and 7-NI (100\u03bcmol l-1) decreased the rotation rate by approximately 50%,whereas co-addition of L-NAME and SNAP caused a twofold increase. In an analysis of the surge and inter-surge subcomponents of the rotational behavior, the NO donors increased the inter-surge rotation rate and the surge amplitude. In contrast, the NO inhibitors decreased the inter-surge rotation rate and the frequency of surges. These data suggest that the embryonic rotational behavior depends in part on the constitutive excitatory actions of NO on ENC1 and ciliary cells.<\/jats:p>","DOI":"10.1242\/jeb.205.20.3143","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T05:00:01Z","timestamp":1619326801000},"page":"3143-3152","source":"Crossref","is-referenced-by-count":20,"title":["Regulation of early embryonic behavior by nitric oxide in the pond snail<i>Helisoma trivolvis<\/i>"],"prefix":"10.1242","volume":"205","author":[{"given":"Alison G.","family":"Cole","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, University of Alberta, Edmonton,Alberta, Canada T6G 2E9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aniseh","family":"Mashkournia","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Alberta, Edmonton,Alberta, Canada T6G 2E9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn C.","family":"Parries","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Alberta, Edmonton,Alberta, Canada T6G 2E9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey I.","family":"Goldberg","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Alberta, Edmonton,Alberta, Canada T6G 2E9"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042504560208700_REF1","doi-asserted-by":"crossref","unstructured":"Arancio, O., Kiebler, M., Lee, C. J., Lev-Ram, V., Tsien, R. Y.,Kandel, E. R. and Hawkins, R. D. (1996). Nitric oxide acts directly in the presynaptic neuron to produce long-term potentiation in cultured hippocampal neurons. Cell87,1025-1035.","DOI":"10.1016\/S0092-8674(00)81797-3"},{"key":"2021042504560208700_REF2","doi-asserted-by":"crossref","unstructured":"Asano, K., Chee, C. B., Gaston, B., Lilly, C. M., Gerard, C.,Drazen, J. M. and Stamler, J. S. (1994). Constitutive and inducible nitric oxide synthase gene expression, regulation, and activity in human lung epithelial cells. Proc. Natl. Acad. Sci. USA91,10089-10093.","DOI":"10.1073\/pnas.91.21.10089"},{"key":"2021042504560208700_REF3","doi-asserted-by":"crossref","unstructured":"Beesley, J. E. (1995). Histochemical methods for detecting nitric oxide synthase. Histochem. J.27,757-769.","DOI":"10.1007\/BF02388301"},{"key":"2021042504560208700_REF4","doi-asserted-by":"crossref","unstructured":"Bicker, G. (2001). Nitric oxide: An unconventional messenger in the nervous system of an orthopteroid insect. Arch. Insect. Biochem. Physiol.48,100-110.","DOI":"10.1002\/arch.1062"},{"key":"2021042504560208700_REF5","doi-asserted-by":"crossref","unstructured":"Blottner, D., Grozdanovic, Z. and Gossrau, R.(1995). Histochemistry of nitric oxide synthase in the nervous system. Histochem. J.27,785-811.","DOI":"10.1007\/BF02388304"},{"key":"2021042504560208700_REF6","doi-asserted-by":"crossref","unstructured":"Breer, H. and Shepherd, G. M. (1993). Implications of the NO\/cGMP system for olfaction. Trends Neurosci.16,5-9.","DOI":"10.1016\/0166-2236(93)90040-S"},{"key":"2021042504560208700_REF7","doi-asserted-by":"crossref","unstructured":"Cheung, W. S., Bhan, I. and Lipton, S. A.(2000). Nitric oxide (NO) stabilizes whereas nitrosonium(NO+) enhances filopodial outgrowth by rat retinal ganglion cells in vitro. Brain Res.868, 1-13.","DOI":"10.1016\/S0006-8993(00)02161-2"},{"key":"2021042504560208700_REF8","doi-asserted-by":"crossref","unstructured":"Christopher, K. J., Chang, J. P. and Goldberg, J. I.(1996). Stimulation of cilia beat frequency by serotonin is mediated by a calcium influx in ciliated cells of H. trivolvisembryos. J. Exp. Biol.199,1105-1113.","DOI":"10.1242\/jeb.199.5.1105"},{"key":"2021042504560208700_REF9","unstructured":"Christopher, K. J., Young, K. G., Chang, J. P. and Goldberg, J. I. (1999). Involvement of protein kinase C in 5-HT-stimulated ciliary activity in H. trivolvis embryos. J. Physiol.515,511-522."},{"key":"2021042504560208700_REF10","doi-asserted-by":"crossref","unstructured":"Clementi, E. (1998). Role of nitric oxide and its intracellular signalling pathways in the control of Ca2+homeostasis. Biochem. Pharmacol.55,713-718.","DOI":"10.1016\/S0006-2952(97)00375-4"},{"key":"2021042504560208700_REF11","doi-asserted-by":"crossref","unstructured":"Colasanti, M. and Venturini, G. (1998). Nitric oxide in invertebrates. Mol. Neurobiol.17,157-174.","DOI":"10.1007\/BF02802029"},{"key":"2021042504560208700_REF12","doi-asserted-by":"crossref","unstructured":"Diefenbach, T. J., Koehncke, N. K. and Goldberg, J. I.(1991). Characterization and development of rotational behavior in Helisoma embryos: role of endogenous serotonin. J. Neurobiol.22,922-934.","DOI":"10.1002\/neu.480220905"},{"key":"2021042504560208700_REF13","unstructured":"Diefenbach, T. J., Koss, R. and Goldberg, J. I.(1998). Early development of an identified serotonergic neuron in H. trivolvis embryos: serotonin expression, de-expression, and uptake. J. Neurobiol.34,361-376."},{"key":"2021042504560208700_REF14","doi-asserted-by":"crossref","unstructured":"Diefenbach, T. J., Sloley, B. D. and Goldberg, J. I.(1995). Neurite branch development of an identified serotonergic neuron from embryonic Helisoma: evidence for autoregulation by serotonin. Dev. Biol.167,282-293.","DOI":"10.1006\/dbio.1995.1023"},{"key":"2021042504560208700_REF15","doi-asserted-by":"crossref","unstructured":"Elphick, M. R., Kemenes, G., Staras, K. and O'Shea, M.(1995). Behavioral role for nitric oxide in chemosensory activation of feeding in a mollusc. J. Neurosci.15,7653-7664.","DOI":"10.1523\/JNEUROSCI.15-11-07653.1995"},{"key":"2021042504560208700_REF16","doi-asserted-by":"crossref","unstructured":"Ernst, A. F., Gallo, G., Letourneau, P. C. and McLoon, S. C.(2000). Stabilization of growing retinal axons by the combined signaling of nitric oxide and brain-derived neurotrophic factor. J. Neurosci.20,1458-1469.","DOI":"10.1523\/JNEUROSCI.20-04-01458.2000"},{"key":"2021042504560208700_REF17","doi-asserted-by":"crossref","unstructured":"Froggett, S. J. and Leise, E. M. (1999). Metamorphosis in the marine snail Ilyanassa obsoleta, yes or NO?Biol. Bull. 196,57-62.","DOI":"10.2307\/1543167"},{"key":"2021042504560208700_REF18","doi-asserted-by":"crossref","unstructured":"Gelperin, A., Flores, J., Raccuia-Behling, F. and Cooke, I. R. (2000). Nitric oxide and carbon monoxide modulate oscillations of olfactory interneurons in a terrestrial mollusk. J. Neurophysiol.83,116-127.","DOI":"10.1152\/jn.2000.83.1.116"},{"key":"2021042504560208700_REF19","doi-asserted-by":"crossref","unstructured":"Gendron, L., Cote, F., Payet, M. D. and Gallo-Payet, N.(2002). Nitric oxide and cyclic GMP are involved in angiotensin II AT(2) receptor effects on neurite outgrowth in NG108-15 cells. Neuroendocrinol.75,70-81.","DOI":"10.1159\/000048222"},{"key":"2021042504560208700_REF20","unstructured":"Goldberg, J. I. (1995). Neuronal development in embryos of the mollusk, H. trivolvis: multiple roles of serotonin. Adv. Neur. Sci.2,67-87."},{"key":"2021042504560208700_REF21","unstructured":"Goldberg, J. I., Cole, A., Mashkournia, A., Crowe, A., Robbins,S. and Uretsky, A. (1999). Expression and function of nitric oxide in embryos of the pond snail, H. trivolvis.Soc. Neurosci. abstr.25,679.5."},{"key":"2021042504560208700_REF22","doi-asserted-by":"crossref","unstructured":"Goldberg, J. I. and Kater, S. B. (1989). Expression and function of the neurotransmitter serotonin during development of the Helisoma nervous system. Dev. Biol.131,483-495.","DOI":"10.1016\/S0012-1606(89)80019-3"},{"key":"2021042504560208700_REF23","doi-asserted-by":"crossref","unstructured":"Goldberg, J. I., Koehncke, N. K., Christopher, K. J., Neumann,C. and Diefenbach, T. J. (1994). Pharmacological characterization of a serotonin receptor involved in an early embryonic behavior of H. trivolvis.J. Neurobiol.25,1545-1557.","DOI":"10.1002\/neu.480251207"},{"key":"2021042504560208700_REF24","unstructured":"Goldberg, J. I., McCobb, D. P., Guthrie, P. B., Lawton, R. A.,Lee, R. E. and Kater, S. B. (1988). Characterization of cultured embryonic neurons from the snail Helisoma. In Cell Culture Approaches to Invertebrate Neuroscience(ed. D. Beadle, G. Lees and S. B. Kater), pp. 85-108. London: Academic Press Inc."},{"key":"2021042504560208700_REF25","unstructured":"Goldberg, J. I., Tran, N., Doran, S. A., Ahn, K.-C. and Mashkournia, A. (2000). Regulation of ciliary beating by nitric oxide in cultured ciliated cells from H. trivolvis embryos. Soc. Neurosci. Abstr.26, 437.1."},{"key":"2021042504560208700_REF26","doi-asserted-by":"crossref","unstructured":"Hindley, S., Juurlink, B. H., Gysbers, J. W., Middlemiss, P. J.,Herman, M. A. and Rathbone, M. P. (1997). Nitric oxide donors enhance neurotrophin-induced neurite outgrowth through a cGMP-dependent mechanism. J. Neurosci. Res.47,427-439.","DOI":"10.1002\/(SICI)1097-4547(19970215)47:4<427::AID-JNR8>3.0.CO;2-G"},{"key":"2021042504560208700_REF27","doi-asserted-by":"crossref","unstructured":"Jacklet, J. W. (1997). Nitric oxide signaling in invertebrates. Invert. Neurosci.3, 1-14.","DOI":"10.1007\/BF02481710"},{"key":"2021042504560208700_REF28","doi-asserted-by":"crossref","unstructured":"Kempf, S. C., Page, L. and Pires, A. (1997). Development of serotonin-like immunoreactivity in the embryos and larvae of nudibranch mollusks with emphasis on the structure and possible function of the apical sensory organ. J. Comp. Neurol.386,507-528.","DOI":"10.1002\/(SICI)1096-9861(19970929)386:3<507::AID-CNE12>3.0.CO;2-7"},{"key":"2021042504560208700_REF29","doi-asserted-by":"crossref","unstructured":"Koh, H. Y. and Jacklet, J. W. (2001). Nitric oxide induces cGMP immunoreactivity and modulates membrane conductance in identified central neurons of Aplysia.Eur. J. Neurosci.13,553-560.","DOI":"10.1046\/j.0953-816x.2000.01416.x"},{"key":"2021042504560208700_REF30","unstructured":"Koss, R., Diefenbach, T. J., Kuang, S., Doran, S. A. and Goldberg, J. I. (2002). Coordinated development of identified serotonergic neurons and their target ciliary cells in H. trivolvisembryos. J. Comp. Neurol., in press."},{"key":"2021042504560208700_REF31","doi-asserted-by":"crossref","unstructured":"Kuang, S., Doran, S. A., Wilson, R. J. A., Goss, G. G. and Goldberg, J. I. (2002). Serotonergic sensorimotor neurons mediate a behavioral response to hypoxia in pond snail embryos. J. Neurobiol.52,73-83.","DOI":"10.1002\/neu.10071"},{"key":"2021042504560208700_REF32","doi-asserted-by":"crossref","unstructured":"Kuang, S. and Goldberg, J. I. (2001). Laser ablation reveals regulation of ciliary activity by serotonergic neurons in molluscan embryos. J. Neurobiol.47, 1-15.","DOI":"10.1002\/neu.1011"},{"key":"2021042504560208700_REF33","unstructured":"Leise, E. M., Thavaradhara, K., Durham, N. R. and Turner, B. E. (2001). Serotonin and nitric oxide regulate metamorphosis in the marine snail Ilyanassa obsoleta.Amer. Zool.41,258-267."},{"key":"2021042504560208700_REF34","doi-asserted-by":"crossref","unstructured":"Li, D., Shirakami, G., Zhan, X. and Johns, R. A.(2000). Regulation of ciliary beat frequency by the nitric oxide\u2014cyclic guanosine monophosphate signaling pathway in rat airway epithelial cells. Am. J. Respir. Cell Mol. Biol.23,175-181.","DOI":"10.1165\/ajrcmb.23.2.4022"},{"key":"2021042504560208700_REF35","doi-asserted-by":"crossref","unstructured":"Lin, M. and Leise, E. M. (1996). NADPH-diaphorase activity changes during gangliogenesis and metamorphosis in the gastropod mollusc Ilyanassa obsoleta.J. Comp. Neurol.374,194-203.","DOI":"10.1002\/(SICI)1096-9861(19961014)374:2<194::AID-CNE3>3.0.CO;2-Y"},{"key":"2021042504560208700_REF36","doi-asserted-by":"crossref","unstructured":"Martinez, A. (1995). Nitric oxide synthase in invertebrates. Histochem. J.27,770-776.","DOI":"10.1007\/BF02388302"},{"key":"2021042504560208700_REF37","unstructured":"Meleshkevitch, E. A., Budko, D., Norby, S., Moroz, L. and Hadfield, M. (1997). Nitric oxide-dependent modulation of the metamorphosis in mollusc Phestilla sibogae.Soc. Neurosci. abstr.23,1233."},{"key":"2021042504560208700_REF38","doi-asserted-by":"crossref","unstructured":"Moroz, L. L., Park, J. H. and Winlow, W.(1993). Nitric oxide activates buccal motor patterns in Lymnaea stagnalis.Neuroreport4, 643-646.","DOI":"10.1097\/00001756-199306000-00010"},{"key":"2021042504560208700_REF39","doi-asserted-by":"crossref","unstructured":"Moroz, L. L., Winlow, W., Turner, R. W., Bulloch, A. G.,Lukowiak, K. and Syed, N. I. (1994). Nitric oxide synthase-immunoreactive cells in the CNS and periphery of Lymnaea.Neuroreport5,1277-1280.","DOI":"10.1097\/00001756-199406020-00031"},{"key":"2021042504560208700_REF40","doi-asserted-by":"crossref","unstructured":"Moroz, L. L. (2000). Giant identified NO-releasing neurons and comparative histochemistry of putative nitrergic systems in gastropod molluscs. Microsc. Res. Tech.49,557-569.","DOI":"10.1002\/1097-0029(20000615)49:6<557::AID-JEMT6>3.0.CO;2-S"},{"key":"2021042504560208700_REF41","doi-asserted-by":"crossref","unstructured":"Page, L. R. and Parries, S. C. (2000). Comparative study of the apical ganglion in planktotrophic caenogastropod larvae: ultrastructure and immunoreactivity to serotonin. J. Comp. Neurol.418,383-401.","DOI":"10.1002\/(SICI)1096-9861(20000320)418:4<383::AID-CNE2>3.0.CO;2-B"},{"key":"2021042504560208700_REF42","doi-asserted-by":"crossref","unstructured":"Park, J., Straub, V. A. and O'Shea, M. (1998). Anterograde signaling by nitric oxide: characterization and in vitro reconstitution of an identified nitrergic synapse. J. Neurosci.18,5463-5476.","DOI":"10.1523\/JNEUROSCI.18-14-05463.1998"},{"key":"2021042504560208700_REF43","doi-asserted-by":"crossref","unstructured":"Philippides, A., Husbands, P. and O'Shea, M.(2000). Four-dimensional neuronal signaling by nitric oxide: a computational analysis. J. Neurosci.20,1199-1207.","DOI":"10.1523\/JNEUROSCI.20-03-01199.2000"},{"key":"2021042504560208700_REF44","doi-asserted-by":"crossref","unstructured":"Salathe, M., Lieb, T. and Bookman, R. J.(2000). Lack of nitric oxide involvement in cholinergic modulation of ovine ciliary beat frequency. J. Aerosol. Med.13,219-29.","DOI":"10.1089\/jam.2000.13.219"},{"key":"2021042504560208700_REF45","doi-asserted-by":"crossref","unstructured":"Schmachtenberg, O. and Bacigalupo, J. (1999). Nitric oxide activates a potassium current in olfactory receptor neurons from Caudiverbera caudiverbera and Xenopus laevis.Brain Res.837,301-305.","DOI":"10.1016\/S0006-8993(99)01635-2"},{"key":"2021042504560208700_REF46","doi-asserted-by":"crossref","unstructured":"Seidel, C. and Bicker, G. (2000). Nitric oxide and cGMP influence axonogenesis of antennal pioneer neurons. Development127,4541-4549.","DOI":"10.1242\/dev.127.21.4541"},{"key":"2021042504560208700_REF47","unstructured":"Serfo\u0308zo\u0308, Z., Elekes, K. and Varga, V.(1998). NADPH-diaphorase activity in the nervous system of the embryonic and juvenile pond snail, Lymnaea stagnalis.Cell Tissue Res.292,579-586."},{"key":"2021042504560208700_REF48","doi-asserted-by":"crossref","unstructured":"Sisson, J. H. (1995). Ethanol stimulates apparent nitric oxide-dependent ciliary beat frequency in bovine airway epithelial cells. Amer. J. Physiol.12,L596-L600.","DOI":"10.1152\/ajplung.1995.268.4.L596"},{"key":"2021042504560208700_REF49","doi-asserted-by":"crossref","unstructured":"Uzlaner, N. and Priel, Z. (1999). Interplay between the NO pathway and elevated [Ca2+]i enhances ciliary activity in rabbit trachea. J. Physiol.516,179-190.","DOI":"10.1111\/j.1469-7793.1999.179aa.x"},{"key":"2021042504560208700_REF50","doi-asserted-by":"crossref","unstructured":"Van Wagenen, S. and Rehder, V. (1999). Regulation of neuronal growth cone filopodia by nitric oxide. J. Neurobiol.39,168-185.","DOI":"10.1002\/(SICI)1097-4695(199905)39:2<168::AID-NEU2>3.0.CO;2-F"},{"key":"2021042504560208700_REF51","doi-asserted-by":"crossref","unstructured":"Van Wagenen, S. and Rehder, V. (2001). Regulation of neuronal growth cone filopodia by nitric oxide depends on soluble guanylyl cyclase. J. Neurobiol.46,206-219.","DOI":"10.1002\/1097-4695(20010215)46:3<206::AID-NEU1003>3.0.CO;2-S"},{"key":"2021042504560208700_REF52","doi-asserted-by":"crossref","unstructured":"Wright, J. W., Schwinof, K. M., Snyder, M. A. and Copenhaver, P. F. (1998). A delayed role for nitric oxide-sensitive guanylate cyclases in a migratory population of embryonic neurons. Dev. Biol.204,15-33.","DOI":"10.1006\/dbio.1998.9066"},{"key":"2021042504560208700_REF53","doi-asserted-by":"crossref","unstructured":"Xue, C., Botkin, S. J. and Johns, R. A. (1996). Localization of endothelial NOS at the basal microtubule membrane in ciliated epithelium of rat lung. J. Histochem. Cytochem.44,463-471.","DOI":"10.1177\/44.5.8627003"}],"container-title":["Journal of Experimental Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/jeb\/article-pdf\/205\/20\/3143\/1241652\/3143.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jeb\/article-pdf\/205\/20\/3143\/1241652\/3143.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,25]],"date-time":"2022-12-25T10:39:12Z","timestamp":1671964752000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jeb\/article\/205\/20\/3143\/9037\/Regulation-of-early-embryonic-behavior-by-nitric"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,10,15]]},"references-count":53,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2002,10,15]]}},"URL":"https:\/\/doi.org\/10.1242\/jeb.205.20.3143","relation":{},"ISSN":["1477-9145","0022-0949"],"issn-type":[{"value":"1477-9145","type":"electronic"},{"value":"0022-0949","type":"print"}],"subject":[],"published":{"date-parts":[[2002,10,15]]}}}