{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:20:30Z","timestamp":1790076030741,"version":"4.0.1"},"reference-count":76,"publisher":"Society for Neuroscience","issue":"1","license":[{"start":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T00:00:00Z","timestamp":1593648000000},"content-version":"vor","delay-in-days":241,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2020,1,2]]},"abstract":"<jats:p>Down syndrome cell adhesion molecules (<jats:italic>dscam<\/jats:italic>and<jats:italic>dscaml1<\/jats:italic>) are essential regulators of neural circuit assembly, but their roles in vertebrate neural circuit function are still mostly unexplored. We investigated the functional consequences of<jats:italic>dscaml1<\/jats:italic>deficiency in the larval zebrafish (sexually undifferentiated) oculomotor system, where behavior, circuit function, and neuronal activity can be precisely quantified. Genetic perturbation of<jats:italic>dscaml1<\/jats:italic>resulted in deficits in retinal patterning and light adaptation, consistent with its known roles in mammals. Oculomotor analyses revealed specific deficits related to the<jats:italic>dscaml1<\/jats:italic>mutation, including severe fatigue during gaze stabilization, reduced saccade amplitude and velocity in the light, greater disconjugacy, and impaired fixation. Two-photon calcium imaging of abducens neurons in control and<jats:italic>dscaml1<\/jats:italic>mutant animals confirmed deficits in saccade-command signals (indicative of an impairment in the saccadic premotor pathway), whereas abducens activation by the pretectum-vestibular pathway was not affected. Together, we show that loss of<jats:italic>dscaml1<\/jats:italic>resulted in impairments in specific oculomotor circuits, providing a new animal model to investigate the development of oculomotor premotor pathways and their associated human ocular disorders.<\/jats:p><jats:p><jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold><jats:italic>Dscaml1<\/jats:italic>is a neural developmental gene with unknown behavioral significance. Using the zebrafish model, this study shows that<jats:italic>dscaml1<\/jats:italic>mutants have a host of oculomotor (eye movement) deficits. Notably, the oculomotor phenotypes in<jats:italic>dscaml1<\/jats:italic>mutants are reminiscent of human ocular motor apraxia, a neurodevelopmental disorder characterized by reduced saccade amplitude and gaze stabilization deficits. Population-level recording of neuronal activity further revealed potential subcircuit-specific requirements for<jats:italic>dscaml1<\/jats:italic>during oculomotor behavior. These findings underscore the importance of<jats:italic>dscaml1<\/jats:italic>in the development of visuomotor function and characterize a new model to investigate potential circuit deficits underlying human oculomotor disorders.<\/jats:p>","DOI":"10.1523\/jneurosci.1783-19.2019","type":"journal-article","created":{"date-parts":[[2019,11,4]],"date-time":"2019-11-04T22:52:25Z","timestamp":1572907945000},"page":"143-158","source":"Crossref","is-referenced-by-count":19,"title":["Zebrafish<i>dscaml1<\/i>Deficiency Impairs Retinal Patterning and Oculomotor Function"],"prefix":"10.1523","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1905-3615","authenticated-orcid":false,"given":"Manxiu","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandro D.","family":"Ramirez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel L.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine E.","family":"Harmon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Schoppik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avirale","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Kuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie L.","family":"Goei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Gagnon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Zimmerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengdar Q.","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Reyon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Keith","family":"Joung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4561-4175","authenticated-orcid":false,"given":"Emre R.F.","family":"Aksay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander F.","family":"Schier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6485-5487","authenticated-orcid":false,"given":"Y. Albert","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2019,11,4]]},"reference":[{"key":"2023041803391812000_40.1.143.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2012.273"},{"key":"2023041803391812000_40.1.143.2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00311.2004"},{"key":"2023041803391812000_40.1.143.3","doi-asserted-by":"publisher","DOI":"10.1067\/mpd.2000.106225"},{"key":"2023041803391812000_40.1.143.4","doi-asserted-by":"publisher","DOI":"10.3389\/fnsys.2011.00101"},{"key":"2023041803391812000_40.1.143.5","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S45931"},{"key":"2023041803391812000_40.1.143.6","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6015-10.2011"},{"key":"2023041803391812000_40.1.143.7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1618606114"},{"key":"2023041803391812000_40.1.143.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(05)51001-X"},{"key":"2023041803391812000_40.1.143.9","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1987.57.5.1383"},{"key":"2023041803391812000_40.1.143.10","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.258640"},{"key":"2023041803391812000_40.1.143.11","doi-asserted-by":"publisher","DOI":"10.3389\/fnsys.2016.00080"},{"key":"2023041803391812000_40.1.143.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.01.006"},{"key":"2023041803391812000_40.1.143.13","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2302(199712)31:4<267::AID-DEV4>3.0.CO;2-P"},{"key":"2023041803391812000_40.1.143.14","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1480-18.2018"},{"key":"2023041803391812000_40.1.143.15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709337104"},{"key":"2023041803391812000_40.1.143.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.05.016"},{"key":"2023041803391812000_40.1.143.17","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21381"},{"key":"2023041803391812000_40.1.143.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.09.027"},{"key":"2023041803391812000_40.1.143.19","first-page":"443","article-title":"Expression patterns of dscam and sdk gene paralogs in developing zebrafish retina","volume":"24","author":"Galicia","year":"2018","journal-title":"Mol Vis"},{"key":"2023041803391812000_40.1.143.20","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.85.12.1477"},{"key":"2023041803391812000_40.1.143.21","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2012.00086"},{"key":"2023041803391812000_40.1.143.22","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.16144"},{"key":"2023041803391812000_40.1.143.23","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.80.2.151"},{"key":"2023041803391812000_40.1.143.24","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-01-00206.2000"},{"key":"2023041803391812000_40.1.143.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2014.06.003"},{"key":"2023041803391812000_40.1.143.26","doi-asserted-by":"publisher","DOI":"10.1038\/nature13908"},{"key":"2023041803391812000_40.1.143.27","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200707090"},{"key":"2023041803391812000_40.1.143.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.09.048"},{"key":"2023041803391812000_40.1.143.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.09.055"},{"key":"2023041803391812000_40.1.143.30","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1002030302"},{"key":"2023041803391812000_40.1.143.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.02.043"},{"key":"2023041803391812000_40.1.143.32","doi-asserted-by":"publisher","DOI":"10.1186\/1749-8104-6-10"},{"key":"2023041803391812000_40.1.143.33","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3045-14.2015"},{"key":"2023041803391812000_40.1.143.34","doi-asserted-by":"crossref","unstructured":"Leigh RJ , Zee DS (2015) The neurology of eye movements, Ed 5. Oxford: Oxford UP.","DOI":"10.1093\/med\/9780199969289.001.0001"},{"key":"2023041803391812000_40.1.143.35","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi264"},{"key":"2023041803391812000_40.1.143.36","doi-asserted-by":"publisher","DOI":"10.1046\/j.1095-8649.2003.00074.x"},{"key":"2023041803391812000_40.1.143.37","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2009.03854.x"},{"key":"2023041803391812000_40.1.143.38","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1403105111"},{"key":"2023041803391812000_40.1.143.39","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2848-10.2010"},{"key":"2023041803391812000_40.1.143.40","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2811-12.2012"},{"key":"2023041803391812000_40.1.143.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.visres.2003.10.015"},{"key":"2023041803391812000_40.1.143.42","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00702.2010"},{"key":"2023041803391812000_40.1.143.43","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2888"},{"key":"2023041803391812000_40.1.143.44","doi-asserted-by":"publisher","DOI":"10.3791\/3556"},{"key":"2023041803391812000_40.1.143.45","doi-asserted-by":"publisher","DOI":"10.1186\/1749-8104-3-36"},{"key":"2023041803391812000_40.1.143.46","doi-asserted-by":"publisher","DOI":"10.1242\/dev.076588"},{"key":"2023041803391812000_40.1.143.47","doi-asserted-by":"publisher","DOI":"10.1242\/dev.094631"},{"key":"2023041803391812000_40.1.143.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.09.065"},{"key":"2023041803391812000_40.1.143.49","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4332-06.2006"},{"key":"2023041803391812000_40.1.143.50","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3581"},{"key":"2023041803391812000_40.1.143.51","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2170"},{"key":"2023041803391812000_40.1.143.52","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-0682"},{"key":"2023041803391812000_40.1.143.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2014.07.080"},{"key":"2023041803391812000_40.1.143.54","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.12-02-00467.1992"},{"key":"2023041803391812000_40.1.143.55","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(97)83048-5"},{"key":"2023041803391812000_40.1.143.56","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-015-0543-3"},{"key":"2023041803391812000_40.1.143.57","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1934"},{"key":"2023041803391812000_40.1.143.58","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2017.10.012"},{"key":"2023041803391812000_40.1.143.59","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"2023041803391812000_40.1.143.60","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19990222)404:4<515::AID-CNE8>3.0.CO;2-A"},{"key":"2023041803391812000_40.1.143.61","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5193-09.2010"},{"key":"2023041803391812000_40.1.143.62","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1711-17.2017"},{"key":"2023041803391812000_40.1.143.63","doi-asserted-by":"publisher","DOI":"10.1017\/S0952523806230219"},{"key":"2023041803391812000_40.1.143.64","doi-asserted-by":"publisher","DOI":"10.1007\/s00221-001-0912-9"},{"key":"2023041803391812000_40.1.143.65","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00584.2005"},{"key":"2023041803391812000_40.1.143.66","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.12.013"},{"key":"2023041803391812000_40.1.143.67","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00334.2006"},{"key":"2023041803391812000_40.1.143.68","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.06.028"},{"key":"2023041803391812000_40.1.143.69","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3040"},{"key":"2023041803391812000_40.1.143.70","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3339-10.2011"},{"key":"2023041803391812000_40.1.143.71","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4657-04.2005"},{"key":"2023041803391812000_40.1.143.72","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.114.169284"},{"key":"2023041803391812000_40.1.143.73","doi-asserted-by":"publisher","DOI":"10.1038\/nature06469"},{"key":"2023041803391812000_40.1.143.74","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/100.3.581"},{"key":"2023041803391812000_40.1.143.75","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2014.10.060"},{"key":"2023041803391812000_40.1.143.76","doi-asserted-by":"publisher","DOI":"10.1186\/1749-8104-1-2"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.1783-19.2019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T11:50:32Z","timestamp":1681818632000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.1783-19.2019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,4]]},"references-count":76,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1,2]]},"published-print":{"date-parts":[[2020,1,2]]}},"alternative-id":["10.1523\/JNEUROSCI.1783-19.2019"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.1783-19.2019","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,4]]}}}