{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T13:25:41Z","timestamp":1762608341073,"version":"3.41.2"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R25 GM056901","R01 NS110915","R03 HD098555"],"award-info":[{"award-number":["R25 GM056901","R01 NS110915","R03 HD098555"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neural Circuits"],"abstract":"<jats:p>Precise positioning of neurons resulting from cell division and migration during development is critical for normal brain function. Disruption of neuronal migration can cause a myriad of neurological disorders. To investigate the functional consequences of defective neuronal positioning on circuit function, we studied a zebrafish <jats:italic>frizzled3a<\/jats:italic> (<jats:italic>fzd3a<\/jats:italic>) loss-of-function mutant <jats:italic>off-limits<\/jats:italic> (<jats:italic>olt<\/jats:italic>) where the facial branchiomotor (FBM) neurons fail to migrate out of their birthplace. A jaw movement assay, which measures the opening of the zebrafish jaw (gape), showed that the frequency of gape events, but not their amplitude, was decreased in <jats:italic>olt<\/jats:italic> mutants. Consistent with this, a larval feeding assay revealed decreased food intake in <jats:italic>olt<\/jats:italic> mutants, indicating that the FBM circuit in mutants generates defective functional outputs. We tested various mechanisms that could generate defective functional outputs in mutants. While <jats:italic>fzd3a<\/jats:italic> is ubiquitously expressed in neural and non-neural tissues, jaw cartilage and muscle developed normally in <jats:italic>olt<\/jats:italic> mutants, and muscle function also appeared to be unaffected. Although FBM neurons were mispositioned in <jats:italic>olt<\/jats:italic> mutants, axon pathfinding to jaw muscles was unaffected. Moreover, neuromuscular junctions established by FBM neurons on jaw muscles were similar between wildtype siblings and <jats:italic>olt<\/jats:italic> mutants. Interestingly, motor axons innervating the interhyoideus jaw muscle were frequently defasciculated in <jats:italic>olt<\/jats:italic> mutants. Furthermore, GCaMP imaging revealed that mutant FBM neurons were less active than their wildtype counterparts. These data show that aberrant positioning of FBM neurons in <jats:italic>olt<\/jats:italic> mutants is correlated with subtle defects in fasciculation and neuronal activity, potentially generating defective functional outputs.<\/jats:p>","DOI":"10.3389\/fncir.2021.690475","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T14:50:16Z","timestamp":1624546216000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Defective Neuronal Positioning Correlates With Aberrant Motor Circuit Function in Zebrafish"],"prefix":"10.3389","volume":"15","author":[{"given":"Emilia","family":"Asante","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Devynn","family":"Hummel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suman","family":"Gurung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasmin M.","family":"Kassim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noor","family":"Al-Shakarji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kannappan","family":"Palaniappan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinoth","family":"Sittaramane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anand","family":"Chandrasekhar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1080\/01677063.2017.1358270","article-title":"Role of branchiomotor neurons in controlling food intake of zebrafish larvae.","volume":"31","author":"Allen","year":"2017","journal-title":"J. Neurogenet"},{"key":"B2","doi-asserted-by":"crossref","first-page":"1707.e5","DOI":"10.1016\/j.cub.2017.05.029","article-title":"Functional interactions between newborn and mature neurons leading to integration into established neuronal circuits.","volume":"27","author":"Boulanger-Weill","year":"2017","journal-title":"Curr. Biol. : CB"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2565","DOI":"10.1242\/jeb.203.17.2565","article-title":"Locomotor repertoire of the larval zebrafish: swimming, turning and prey capture.","volume":"203","author":"Budick","year":"2000","journal-title":"J. Exp. Biol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1242\/jeb.128918","article-title":"Zebrafish learn to forage in the dark.","volume":"219","author":"Carrillo","year":"2016","journal-title":"J. Exp. Biol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1002\/dvdy.10444","article-title":"Turning heads: development of vertebrate branchiomotor neurons.","volume":"229","author":"Chandrasekhar","year":"2004","journal-title":"Dev. Dyn."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2633","DOI":"10.1242\/dev.124.13.2633","article-title":"Development of branchiomotor neurons in zebrafish.","volume":"124","author":"Chandrasekhar","year":"1997","journal-title":"Development"},{"key":"B7","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/s0920-1211(99)00047-9","article-title":"Neuronal migration disorders in humans and in mouse models\u2013an overview.","volume":"36","author":"Copp","year":"1999","journal-title":"Epilepsy Res."},{"key":"B8","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0925-4773(01)00396-3","article-title":"Neuronal migration.","volume":"105","author":"de Rouvroit","year":"2001","journal-title":"Mech. Dev."},{"key":"B9","doi-asserted-by":"crossref","first-page":"R231","DOI":"10.1016\/S0960-9822(06)00108-4","article-title":"Cortical development: layers of complexity.","volume":"7","author":"Gilmore","year":"1997","journal-title":"Curr. Biol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.ydbio.2012.06.021","article-title":"The mouse Wnt\/PCP protein Vangl2 is necessary for migration of facial branchiomotor neurons, and functions independently of Dishevelled.","volume":"369","author":"Glasco","year":"2012","journal-title":"Dev. Biol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/s0166-2236(00)01607-6","article-title":"Neuronal migration disorders: from genetic diseases to developmental mechanisms.","volume":"23","author":"Gleeson","year":"2000","journal-title":"Trends Neurosci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.devcel.2011.06.011","article-title":"Planar cell polarity: coordinating morphogenetic cell behaviors with embryonic polarity.","volume":"21","author":"Gray","year":"2011","journal-title":"Dev. Cell"},{"key":"B13","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1038\/nrn2254","article-title":"Patterning and axon guidance of cranial motor neurons.","volume":"8","author":"Guthrie","year":"2007","journal-title":"Nat. Rev. Neurosc"},{"key":"B14","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1523\/JNEUROSCI.20-01-00206.2000","article-title":"Visualization of cranial motor neurons in live transgenic zebrafish expressing green fluorescent protein under the control of the islet-1 promoter\/enhancer.","volume":"20","author":"Higashijima","year":"2000","journal-title":"J. Neurosci"},{"key":"B15","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1006\/dbio.1997.8779","article-title":"High-frequency generation of transgenic zebrafish which reliably express GFP in whole muscles or the whole body by using promoters of zebrafish origin.","volume":"192","author":"Higashijima","year":"1997","journal-title":"Dev. Biol."},{"key":"B16","doi-asserted-by":"crossref","first-page":"E3005","DOI":"10.1073\/pnas.1406399111","article-title":"Frizzled3 is required for the development of multiple axon tracts in the mouse central nervous system.","volume":"111","author":"Hua","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2252","DOI":"10.1002\/cne.22627","article-title":"Localization of Cadm2a and Cadm3 proteins during development of the zebrafish nervous system.","volume":"519","author":"Hunter","year":"2011","journal-title":"J. Comparative Neurol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1242\/jeb.01564","article-title":"Development of oxygen sensing in the gills of zebrafish.","volume":"208","author":"Jonz","year":"2005","journal-title":"J. Exp. Biol"},{"key":"B19","first-page":"943","article-title":"Dissecting branchiomotor neuron circuits in zebrafish - Toward high-throughput automated analysis of jaw movements","author":"Kassim","year":"2018","journal-title":"Proceeding of the2018 IEEE 15th International Symposium on Biomedical Imaging"},{"key":"B20","doi-asserted-by":"crossref","first-page":"R89","DOI":"10.1093\/hmg\/ddg086","article-title":"Lissencephaly and the molecular basis of neuronal migration.","volume":"12","author":"Kato","year":"2003","journal-title":"Hum. Mol. Genet"},{"key":"B21","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/aja.1002030302","article-title":"Stages of embryonic development of the zebrafish.","volume":"203","author":"Kimmel","year":"1995","journal-title":"Dev. Dyn"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1126\/science.274.5290.1109","article-title":"Patterning the vertebrate neuraxis.","volume":"274","author":"Lumsden","year":"1996","journal-title":"Science"},{"key":"B23","first-page":"1129","article-title":"\u201cReversing disorders of neuronal migration and differentiation in animal models,\u201d","author":"Manent","year":"2013","journal-title":"Jasper\u2019s Basic Mechanisms of the Epilepsies"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1002\/dvdy.22283","article-title":"Prickle1b mediates interpretation of migratory cues during zebrafish facial branchiomotor neuron migration.","volume":"239","author":"Mapp","year":"2010","journal-title":"Dev. Dyn"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-3-540-36689-8_1","article-title":"Guiding neuronal cell migrations.","volume":"2","author":"Mar\u00edn","year":"2010","journal-title":"Cold Spring Harbor Perspect. Biol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1746","DOI":"10.1016\/j.cub.2017.05.033","article-title":"Key features of structural and functional organization of zebrafish facial motor neurons are resilient to disruption of neuronal migration.","volume":"27","author":"McArthur","year":"2017","journal-title":"Curr. Biol."},{"key":"B27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13041-015-0164-4","article-title":"Genes and brain malformations associated with abnormal neuron positioning.","volume":"8","author":"Moffat","year":"2015","journal-title":"Mol. Brain"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2015.00074","article-title":"Neuronal migration abnormalities and its possible implications for schizophrenia.","volume":"9","author":"Muraki","year":"2015","journal-title":"Front. Neurosci"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1186\/1471-213X-6-28","article-title":"A zebrafish screen for craniofacial mutants identifies wdr68 as a highly conserved gene required for endothelin-1 expression.","volume":"6","author":"Nissen","year":"2006","journal-title":"BMC Dev. Biol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2019.00205","article-title":"Toward a better understanding of neuronal migration deficits in autism spectrum disorders.","volume":"7","author":"Pan","year":"2019","journal-title":"Front. Cell Dev. Biol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/j.ydbio.2005.06.027","article-title":"Neuromuscular synaptogenesis in wild-type and mutant zebrafish.","volume":"285","author":"Panzer","year":"2005","journal-title":"Dev. Biol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1016\/j.celrep.2017.04.015","article-title":"The emergence of the spatial structure of tectal spontaneous activity is independent of visual inputs.","volume":"19","author":"Pietri","year":"2017","journal-title":"Cell Rep"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1016\/s0002-9440(10)64645-7","article-title":"Synaptic vesicle protein 2, A new neuroendocrine cell marker.","volume":"157","author":"Portela-Gomes","year":"2000","journal-title":"Am. J. Pathol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ydbio.2007.04.043","article-title":"Calcium signaling in vertebrate embryonic patterning and morphogenesis.","volume":"307","author":"Slusarski","year":"2007","journal-title":"Dev. Biol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1007\/bf02980268","article-title":"Moving cell bodies: understanding the migratory mechanism of facial motor neurons.","volume":"30","author":"Song","year":"2007","journal-title":"Arch. Pharm. Res"},{"key":"B36","doi-asserted-by":"publisher","first-page":"269","DOI":"10.5115\/acb.2010.43.4.269","article-title":"Control of neuronal migration through rostral migration stream in mice.","volume":"43","author":"Sun","year":"2010","journal-title":"Anatomy Cell Biol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1038\/npp.2009.115","article-title":"Normal development of brain circuits.","volume":"35","author":"Tau","year":"2010","journal-title":"Neuropsychopharmacology"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031140","article-title":"Brainstem respiratory oscillators develop independently of neuronal migration defects in the Wnt\/PCP mouse mutant looptail.","volume":"7","author":"Thoby-Brisson","year":"2012","journal-title":"PLoS One"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1038\/nn.2354","article-title":"Genetic identification of an embryonic parafacial oscillator coupling to the preBotzinger complex.","volume":"12","author":"Thoby-Brisson","year":"2009","journal-title":"Nat. Neurosci"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1046\/j.1460-9568.2003.02561.x","article-title":"Perinatal maturation of the mouse respiratory rhythm-generator: in vivo and in vitro studies.","volume":"17","author":"Viemari","year":"2003","journal-title":"Eur. J. Neurosci"},{"key":"B41","doi-asserted-by":"publisher","first-page":"2273","DOI":"10.1242\/dev.01810","article-title":"Dual roles of zygotic and maternal Scribble1 in neural migration and convergent extension movements in zebrafish embryos.","volume":"132","author":"Wada","year":"2005","journal-title":"Development"},{"key":"B42","doi-asserted-by":"publisher","first-page":"4749","DOI":"10.1242\/dev.02665","article-title":"Frizzled3a and Celsr2 function in the neuroepithelium to regulate migration of facial motor neurons in the developing zebrafish hindbrain.","volume":"133","author":"Wada","year":"2006","journal-title":"Development"},{"key":"B43","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1523\/jneurosci.3221-05.2006","article-title":"Axonal growth and guidance defects in Frizzled3 Knock-Out Mice: a comparison of diffusion tensor magnetic resonance imaging, neurofilament staining, and genetically directed cell labeling.","volume":"26","author":"Wang","year":"2006","journal-title":"J. Neurosci"},{"key":"B44","doi-asserted-by":"publisher","first-page":"8563","DOI":"10.1523\/jneurosci.22-19-08563.2002","article-title":"Frizzled-3 is required for the development of major fiber tracts in the rostral CNS.","volume":"22","author":"Wang","year":"2002","journal-title":"J. Neurosci."},{"journal-title":"The Zebrafish Book.","year":"1995","author":"Westerfield","key":"B45"}],"container-title":["Frontiers in Neural Circuits"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncir.2021.690475\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T14:50:37Z","timestamp":1624546237000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncir.2021.690475\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,24]]},"references-count":45,"alternative-id":["10.3389\/fncir.2021.690475"],"URL":"https:\/\/doi.org\/10.3389\/fncir.2021.690475","relation":{},"ISSN":["1662-5110"],"issn-type":[{"type":"electronic","value":"1662-5110"}],"subject":[],"published":{"date-parts":[[2021,6,24]]},"article-number":"690475"}}