{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:58:05Z","timestamp":1791302285204,"version":"4.1.0"},"reference-count":42,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":3425,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Summary<\/jats:title><jats:p>Mutations in patatin-like phospholipase domain containing 6 (PNPLA6), also known as neuropathy target esterase (NTE), or SPG39, cause hereditary spastic paraplegia (HSP). Although studies on animal models including mice and Drosophila have extended our understanding of PNPLA6, its role in neural development and HSP is not clearly understood. Here, we generated a vertebrate model of PNPLA6 insufficiency using morpholino oligonucleotide knockdown in zebrafish (Danio rerio). PNPLA6 knockdown results in developmental abnormalities and motor neuron defects including axon truncation and branching. The phenotypes in pnpla6 knockdown morphants can be rescued by introduction of wide type (WT), but not mutant, human PNPLA6 mRNA. Our results also revealed the involvement of BMP signaling in pnpla6 knockdown phenotypes. Taken together, these results demonstrated an important role of PNPLA6 in motor neuron development and implicated overexpression of BMP signaling as the possible mechanism underlying the developmental defects in pnpla6 morphants.<\/jats:p>","DOI":"10.1242\/dmm.009688","type":"journal-article","created":{"date-parts":[[2012,9,21]],"date-time":"2012-09-21T04:44:53Z","timestamp":1348202693000},"source":"Crossref","is-referenced-by-count":34,"title":["Knockdown of pnpla6 protein results in motor neuron defects in zebrafish"],"prefix":"10.1242","author":[{"given":"Yang","family":"Song","sequence":"first","affiliation":[{"name":"Shandong University, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molin","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong University, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Mao","sequence":"additional","affiliation":[{"name":"Shandong University, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Shao","sequence":"additional","affiliation":[{"name":"Shandong University, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baochang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shandong University, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Song","sequence":"additional","affiliation":[{"name":"Shandong University, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changshun","family":"Shao","sequence":"additional","affiliation":[{"name":"Shandong University, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoqin","family":"Gong","sequence":"additional","affiliation":[{"name":"Shandong University, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2012,1,1]]},"reference":[{"key":"2021042513074741700_b1-0060404","doi-asserted-by":"crossref","first-page":"5075","DOI":"10.1073\/pnas.0401030101","article-title":"Brain-specific deletion of neuropathy target esterase\/swisscheese results in neurodegeneration","volume":"101","author":"Akassoglou","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042513074741700_b2-0060404","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1023\/A:1016349232389","article-title":"Preparation of dissociated zebrafish spinal neuron cultures","volume":"23","author":"Andersen","year":"2001","journal-title":"Methods Cell Sci."},{"key":"2021042513074741700_b3-0060404","doi-asserted-by":"crossref","first-page":"8199","DOI":"10.1523\/JNEUROSCI.0979-08.2008","article-title":"Loss of PINK1 function affects development and results in neurodegeneration in zebrafish","volume":"28","author":"Anichtchik","year":"2008","journal-title":"J. Neurosci."},{"key":"2021042513074741700_b4-0060404","doi-asserted-by":"crossref","first-page":"24477","DOI":"10.1074\/jbc.M002921200","article-title":"Membrane association of and critical residues in the catalytic domain of human neuropathy target esterase","volume":"275","author":"Atkins","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2021042513074741700_b5-0060404","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S0361-9230(00)00382-8","article-title":"Control of motor axon guidance in the zebrafish embryo","volume":"53","author":"Beattie","year":"2000","journal-title":"Brain Res. Bull."},{"key":"2021042513074741700_b6-0060404","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.mcn.2010.08.012","article-title":"The effect of HSP-causing mutations in SPG3A and NIPA1 on the assembly, trafficking, and interaction between atlastin-1 and NIPA1","volume":"46","author":"Botzolakis","year":"2011","journal-title":"Mol. Cell. Neurosci."},{"key":"2021042513074741700_b7-0060404","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.cbi.2007.11.014","article-title":"Molecular cloning and expression analysis of cDNA ends of chicken neuropathy target esterase","volume":"172","author":"Chang","year":"2008","journal-title":"Chem. Biol. Interact."},{"key":"2021042513074741700_b8-0060404","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/nrg2680","article-title":"Genetics of motor neuron disorders: new insights into pathogenic mechanisms","volume":"10","author":"Dion","year":"2009","journal-title":"Nat. Rev."},{"key":"2021042513074741700_b9-0060404","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1093\/hmg\/9.16.2443","article-title":"Zebrafish: bridging the gap between development and disease","volume":"9","author":"Dodd","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"2021042513074741700_b10-0060404","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1038\/nn.2662","article-title":"Zebrafish atlastin controls motility and spinal motor axon architecture via inhibition of the BMP pathway","volume":"13","author":"Fassier","year":"2010","journal-title":"Nat. Neurosci."},{"key":"2021042513074741700_b11-0060404","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1242\/dev.123.1.229","article-title":"Neural degeneration mutants in the zebrafish, Danio rerio","volume":"123","author":"Furutani-Seiki","year":"1996","journal-title":"Development"},{"key":"2021042513074741700_b12-0060404","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.bbalip.2005.08.002","article-title":"Neuropathy target esterase and phospholipid deacylation","volume":"1736","author":"Glynn","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"2021042513074741700_b13-0060404","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.toxlet.2005.10.012","article-title":"A mechanism for organophosphate-induced delayed neuropathy","volume":"162","author":"Glynn","year":"2006","journal-title":"Toxicol. Lett."},{"key":"2021042513074741700_b14-0060404","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.toxlet.2010.03.1120","article-title":"Constructs of human neuropathy target esterase catalytic domain containing mutations related to motor neuron disease have altered enzymatic properties","volume":"196","author":"Hein","year":"2010","journal-title":"Toxicol. Lett."},{"key":"2021042513074741700_b15-0060404","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/348728a0","article-title":"Cell-autonomous action of zebrafish spt-1 mutation in specific mesodermal precursors","volume":"348","author":"Ho","year":"1990","journal-title":"Nature"},{"key":"2021042513074741700_b16-0060404","first-page":"759","article-title":"Initiation of organophosphate-induced delayed neuropathy","volume":"4","author":"Johnson","year":"1982","journal-title":"Neurobehav. Toxicol. Teratol."},{"key":"2021042513074741700_b17-0060404","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.bbadis.2010.09.011","article-title":"Zebrafish models for the functional genomics of neurogenetic disorders","volume":"1812","author":"Kabashi","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"2021042513074741700_b18-0060404","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1016\/j.lfs.2005.11.029","article-title":"Purification and characterization of neuropathy target esterase (NTE) from rat brain","volume":"78","author":"Kaur","year":"2006","journal-title":"Life Sci."},{"key":"2021042513074741700_b19-0060404","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":"2021042513074741700_b20-0060404","doi-asserted-by":"crossref","first-page":"7425","DOI":"10.1523\/JNEUROSCI.17-19-07425.1997","article-title":"The swiss cheese mutant causes glial hyperwrapping and brain degeneration in Drosophila","volume":"17","author":"Kretzschmar","year":"1997","journal-title":"J. Neurosci."},{"key":"2021042513074741700_b21-0060404","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.ajhg.2008.11.003","article-title":"A missense mutation in SLC33A1, which encodes the acetyl-CoA transporter, causes autosomal-dominant spastic paraplegia (SPG42)","volume":"83","author":"Lin","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"2021042513074741700_b22-0060404","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1093\/hmg\/ddm138","article-title":"Huntingtin-deficient zebrafish exhibit defects in iron utilization and development","volume":"16","author":"Lumsden","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"2021042513074741700_b23-0060404","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj3320001","article-title":"Neuropathy target esterase and a homologous Drosophila neurodegeneration-associated mutant protein contain a novel domain conserved from bacteria to man","volume":"332","author":"Lush","year":"1998","journal-title":"Biochem. J."},{"key":"2021042513074741700_b24-0060404","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1083\/jcb.200303168","article-title":"Knockdown of the survival motor neuron (Smn) protein in zebrafish causes defects in motor axon outgrowth and pathfinding","volume":"162","author":"McWhorter","year":"2003","journal-title":"J. Cell Biol."},{"key":"2021042513074741700_b25-0060404","doi-asserted-by":"crossref","first-page":"7796","DOI":"10.1523\/JNEUROSCI.17-20-07796.1997","article-title":"Pathfinding by identified zebrafish motoneurons in the absence of muscle pioneers","volume":"17","author":"Melan\u00e7on","year":"1997","journal-title":"J. Neurosci."},{"key":"2021042513074741700_b26-0060404","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1128\/MCB.24.4.1667-1679.2004","article-title":"Placental failure and impaired vasculogenesis result in embryonic lethality for neuropathy target esterase-deficient mice","volume":"24","author":"Moser","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"2021042513074741700_b27-0060404","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1523\/JNEUROSCI.5097-04.2005","article-title":"Loss of Swiss cheese\/neuropathy target esterase activity causes disruption of phosphatidylcholine homeostasis and neuronal and glial death in adult Drosophila","volume":"25","author":"M\u00fchlig-Versen","year":"2005","journal-title":"J. Neurosci."},{"key":"2021042513074741700_b28-0060404","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/0009-2797(93)90067-9","article-title":"The role of neurotoxic esterase (NTE) in the prevention and potentiation of organophosphorus-induced delayed neurotoxicity (OPIDN)","volume":"87","author":"Pope","year":"1993","journal-title":"Chem. Biol. Interact."},{"key":"2021042513074741700_b29-0060404","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.ajhg.2007.12.018","article-title":"Neuropathy target esterase gene mutations cause motor neuron disease","volume":"82","author":"Rainier","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"2021042513074741700_b30-0060404","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/mus.21777","article-title":"Motor neuron disease due to neuropathy target esterase gene mutation: clinical features of the index families","volume":"43","author":"Rainier","year":"2011","journal-title":"Muscle Nerve"},{"key":"2021042513074741700_b31-0060404","doi-asserted-by":"crossref","first-page":"11594","DOI":"10.1523\/JNEUROSCI.3007-09.2009","article-title":"Neuropathy target esterase is required for adult vertebrate axon maintenance","volume":"29","author":"Read","year":"2009","journal-title":"J. Neurosci."},{"key":"2021042513074741700_b32-0060404","doi-asserted-by":"crossref","first-page":"3805","DOI":"10.1093\/hmg\/ddp324","article-title":"The hereditary spastic paraplegia proteins NIPA1, spastin and spartin are inhibitors of mammalian BMP signalling","volume":"18","author":"Tsang","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"2021042513074741700_b33-0060404","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1086\/510782","article-title":"Mutations in the KIAA0196 gene at the SPG8 locus cause hereditary spastic paraplegia","volume":"80","author":"Valdmanis","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"2021042513074741700_b34-0060404","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1242\/dev.123.1.153","article-title":"Mutations affecting somite formation and patterning in the zebrafish, Danio rerio","volume":"123","author":"van Eeden","year":"1996","journal-title":"Development"},{"key":"2021042513074741700_b35-0060404","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/nn1841","article-title":"Drosophila spichthyin inhibits BMP signaling and regulates synaptic growth and axonal microtubules","volume":"10","author":"Wang","year":"2007","journal-title":"Nat. Neurosci."},{"key":"2021042513074741700_b36-0060404","volume-title":"The Zebrafish Book","author":"Westerfield","year":"1995"},{"key":"2021042513074741700_b37-0060404","first-page":"483","article-title":"Acetylcholinesterase and neuropathy target esterase in chickens treated with acephate","volume":"11","author":"Wilson","year":"1990","journal-title":"Neurotoxicology"},{"key":"2021042513074741700_b38-0060404","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1194\/jlr.M600185-JLR200","article-title":"Characterization of the human patatin-like phospholipase family","volume":"47","author":"Wilson","year":"2006","journal-title":"J. Lipid Res."},{"key":"2021042513074741700_b39-0060404","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/ng1131","article-title":"Loss of neuropathy target esterase in mice links organophosphate exposure to hyperactivity","volume":"33","author":"Winrow","year":"2003","journal-title":"Nat. Genet."},{"key":"2021042513074741700_b40-0060404","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.1093\/hmg\/ddl212","article-title":"The microtubule-severing protein Spastin is essential for axon outgrowth in the zebrafish embryo","volume":"15","author":"Wood","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"2021042513074741700_b41-0060404","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/nchembio.2007.54","article-title":"Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism","volume":"4","author":"Yu","year":"2008","journal-title":"Nat. Chem. Biol."},{"key":"2021042513074741700_b42-0060404","doi-asserted-by":"crossref","first-page":"24024","DOI":"10.1074\/jbc.M400830200","article-title":"Neuropathy target esterase and its yeast homologue degrade phosphatidylcholine to glycerophosphocholine in living cells","volume":"279","author":"Zaccheo","year":"2004","journal-title":"J. Biol. Chem."}],"container-title":["Disease Models &amp; Mechanisms"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/dmm\/article-pdf\/6\/2\/404\/1864928\/404.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.009688\/2060859\/dmm_009688v1.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.009688\/2060859\/dmm_009688v1.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T12:41:24Z","timestamp":1643460084000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dmm\/article\/doi\/10.1242\/dmm.009688\/258665\/Knockdown-of-pnpla6-protein-results-in-motor"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1,1]]},"references-count":42,"URL":"https:\/\/doi.org\/10.1242\/dmm.009688","relation":{},"ISSN":["1754-8411","1754-8403"],"issn-type":[{"value":"1754-8411","type":"electronic"},{"value":"1754-8403","type":"print"}],"subject":[],"published":{"date-parts":[[2012,1,1]]},"article-number":"dmm.009688"}}