{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:12:28Z","timestamp":1791112348386,"version":"4.1.0"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2007,4,18]],"date-time":"2007-04-18T00:00:00Z","timestamp":1176854400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0000375","type":"journal-article","created":{"date-parts":[[2007,4,17]],"date-time":"2007-04-17T17:51:59Z","timestamp":1176832319000},"page":"e375","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":50,"title":["Mechanisms of TSC-mediated Control of Synapse Assembly and Axon Guidance"],"prefix":"10.1371","volume":"2","author":[{"given":"Sarah","family":"Knox","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian D.","family":"Dimitroff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie A.","family":"Howe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Arsham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathew C.","family":"Easterday","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas P.","family":"Neufeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"O'Connor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott B.","family":"Selleck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2007,4,18]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.spen.2006.01.009","article-title":"The neurobiology of tuberous sclerosis complex.","volume":"13","author":"KC Ess","year":"2006","journal-title":"Semin Pediatr Neurol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1038\/nn1566","article-title":"Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2.","volume":"8","author":"SF Tavazoie","year":"2005","journal-title":"Nat Neurosci"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1111\/j.1460-9568.2006.04594.x","article-title":"Impaired synaptic plasticity in a rat model of tuberous sclerosis.","volume":"23","author":"C von der Brelie","year":"2006","journal-title":"Eur J Neurosci"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"6264","DOI":"10.1523\/JNEUROSCI.21-16-06264.2001","article-title":"Increasing the number of synapses modifies olfactory perception in Drosophila.","volume":"21","author":"A Acebes","year":"2001","journal-title":"J Neurosci"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1523\/JNEUROSCI.18-03-00999.1998","article-title":"Single neuron mosaics of the drosophila gigas mutant project beyond normal targets and modify behavior.","volume":"18","author":"I Canal","year":"1998","journal-title":"J Neurosci"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/ng1494","article-title":"Dysregulation of the TSC-mTOR pathway in human disease.","volume":"37","author":"K Inoki","year":"2005","journal-title":"Nat Genet"},{"key":"ref7","first-page":"139","article-title":"Genetic analysis of TOR signaling in Drosophila.","volume":"279","author":"TP Neufeld","year":"2004","journal-title":"Curr Top Microbiol Immunol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.semcdb.2005.11.010","article-title":"Development and structure of synaptic contacts in Drosophila.","volume":"17","author":"A Prokop","year":"2006","journal-title":"Semin Cell Dev Biol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.semcdb.2005.11.004","article-title":"The mechanisms and molecules that connect photoreceptor axons to their targets in Drosophila.","volume":"17","author":"JD Mast","year":"2006","journal-title":"Semin Cell Dev Biol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"157","DOI":"10.3109\/01677069409167277","article-title":"The early causal influence of cell size upon synaptic number: the mutant gigas of Drosophila.","volume":"9","author":"IA Meinertzhagen","year":"1994","journal-title":"J Neurogenet"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/ncb995","article-title":"Rheb is an essential regulator of S6K in controlling cell growth in Drosophila.","volume":"5","author":"H Stocker","year":"2003","journal-title":"Nat Cell Biol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/ncb999","article-title":"Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins.","volume":"5","author":"Y Zhang","year":"2003","journal-title":"Nat Cell Biol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/ncb996","article-title":"Rheb promotes cell growth as a component of the insulin\/TOR signalling network.","volume":"5","author":"LJ Saucedo","year":"2003","journal-title":"Nat Cell Biol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S0896-6273(00)81166-6","article-title":"Highwire regulates synaptic growth in Drosophila.","volume":"26","author":"HI Wan","year":"2000","journal-title":"Neuron"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/S0896-6273(04)00073-X","article-title":"Highwire regulates presynaptic BMP signaling essential for synaptic growth.","volume":"41","author":"BD McCabe","year":"2004","journal-title":"Neuron"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.1101\/gad.835000","article-title":"Regulation of cellular growth by the Drosophila target of rapamycin dTOR.","volume":"14","author":"H Zhang","year":"2000","journal-title":"Genes Dev"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S0896-6273(02)00589-5","article-title":"wishful thinking Encodes a BMP Type II Receptor that Regulates Synaptic Growth in Drosophila.","volume":"33","author":"H Aberle","year":"2002","journal-title":"Neuron"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"5457","DOI":"10.1242\/dev.00772","article-title":"Retrograde Gbb signaling through the Bmp type 2 receptor wishful thinking regulates systemic FMRFa expression in Drosophila.","volume":"130","author":"G Marques","year":"2003","journal-title":"Development"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0896-6273(02)00595-0","article-title":"The Drosophila BMP type II receptor Wishful Thinking regulates neuromuscular synapse morphology and function.","volume":"33","author":"G Marques","year":"2002","journal-title":"Neuron"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1101\/gad.901101","article-title":"TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth.","volume":"15","author":"X Gao","year":"2001","journal-title":"Genes Dev"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S0092-8674(01)00333-6","article-title":"Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size.","volume":"105","author":"CJ Potter","year":"2001","journal-title":"Cell"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S0092-8674(01)00332-4","article-title":"The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation.","volume":"105","author":"N Tapon","year":"2001","journal-title":"Cell"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.cell.2004.08.028","article-title":"Temporal control of differentiation by the insulin receptor\/tor pathway in Drosophila.","volume":"119","author":"JM Bateman","year":"2004","journal-title":"Cell"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1006\/dbio.2000.9680","article-title":"Drosophila PTEN regulates cell growth and proliferation through PI3K-dependent and -independent pathways.","volume":"221","author":"X Gao","year":"2000","journal-title":"Dev Biol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"5365","DOI":"10.1242\/dev.126.23.5365","article-title":"PTEN affects cell size, cell proliferation and apoptosis during Drosophila eye development.","volume":"126","author":"H Huang","year":"1999","journal-title":"Development"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"3244","DOI":"10.1101\/gad.13.24.3244","article-title":"Drosophila tumor suppressor PTEN controls cell size and number by antagonizing the Chico\/PI3-kinase signaling pathway.","volume":"13","author":"DC Goberdhan","year":"1999","journal-title":"Genes Dev"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"3971","DOI":"10.1038\/sj.onc.1203739","article-title":"The conserved PI3'K\/PTEN\/Akt signaling pathway regulates both cell size and survival in Drosophila.","volume":"19","author":"SE Scanga","year":"2000","journal-title":"Oncogene"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0092-8674(00)80657-1","article-title":"gigas, a Drosophila homolog of tuberous sclerosis gene product-2, regulates the cell cycle.","volume":"96","author":"N Ito","year":"1999","journal-title":"Cell"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.neuron.2006.03.023","article-title":"Pten regulates neuronal arborization and social interaction in mice.","volume":"50","author":"CH Kwon","year":"2006","journal-title":"Neuron"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.brainres.2006.05.013","article-title":"S6k1 is not required for Pten-deficient neuronal hypertrophy.","volume":"1100","author":"N Chalhoub","year":"2006","journal-title":"Brain Res"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"10199","DOI":"10.1523\/JNEUROSCI.1223-06.2006","article-title":"Age-independent synaptogenesis by phosphoinositide 3 kinase.","volume":"26","author":"A Martin-Pena","year":"2006","journal-title":"J Neurosci"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1074\/jbc.M310208200","article-title":"Pam and its ortholog highwire interact with and may negatively regulate the TSC1.TSC2 complex.","volume":"279","author":"V Murthy","year":"2004","journal-title":"J Biol Chem"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.cell.2006.01.016","article-title":"TOR signaling in growth and metabolism.","volume":"124","author":"S Wullschleger","year":"2006","journal-title":"Cell"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/S0896-6273(02)00721-3","article-title":"Dynactin is necessary for synapse stabilization.","volume":"34","author":"BA Eaton","year":"2002","journal-title":"Neuron"},{"key":"ref35","article-title":"Lim kinase regulates the development of olfactory and neuromuscular synapses.","author":"LH Ang","year":"2006","journal-title":"Dev Biol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0896-6273(04)00016-9","article-title":"Nervous wreck, an SH3 adaptor protein that interacts with Wsp, regulates synaptic growth in Drosophila.","volume":"41","author":"IP Coyle","year":"2004","journal-title":"Neuron"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"80","DOI":"10.7150\/ijbs.1.80","article-title":"Dissecting Nck\/Dock Signaling Pathways in Drosophila Visual System.","volume":"1","author":"Y Rao","year":"2005","journal-title":"Int J Biol Sci"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1146\/annurev.cellbio.18.031802.150501","article-title":"Actin cytoskeleton regulation in neuronal morphogenesis and structural plasticity.","volume":"18","author":"L Luo","year":"2002","journal-title":"Annu Rev Cell Dev Biol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1038\/ng1430","article-title":"BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling.","volume":"36","author":"XC He","year":"2004","journal-title":"Nat Genet"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1101\/gad.239102","article-title":"Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6K signaling.","volume":"16","author":"T Radimerski","year":"2002","journal-title":"Genes Dev"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"6584","DOI":"10.1002\/j.1460-2075.1996.tb01049.x","article-title":"The Drosophila phosphoinositide 3-kinase Dp110 promotes cell growth.","volume":"15","author":"SJ Leevers","year":"1996","journal-title":"Embo J"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1101\/gad.8.15.1787","article-title":"Distinct morphogenetic functions of similar small GTPases: Drosophila Drac1 is involved in axonal outgrowth and myoblast fusion.","volume":"8","author":"L Luo","year":"1994","journal-title":"Genes Dev"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1126\/science.285.5436.2126","article-title":"Drosophila S6 kinase: a regulator of cell size.","volume":"285","author":"J Montagne","year":"1999","journal-title":"Science"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1534\/genetics.105.051979","article-title":"Drosophila target of rapamycin kinase functions as a multimer.","volume":"172","author":"Y Zhang","year":"2006","journal-title":"Genetics"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1242\/dev.127.4.851","article-title":"Analysis of Drosophila photoreceptor axon guidance in eye-specific mosaics.","volume":"127","author":"TP Newsome","year":"2000","journal-title":"Development"},{"key":"ref46","first-page":"159","article-title":"Imaginal Discs.","author":"SS Blair","year":"2000"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1002\/neu.10189","article-title":"Drosophila neuromuscular synapse assembly and function require the TGF-beta type I receptor saxophone and the transcription factor Mad.","volume":"55","author":"JM Rawson","year":"2003","journal-title":"J Neurobiol"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0000375","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T16:56:19Z","timestamp":1628787379000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0000375"}},"subtitle":[],"editor":[{"given":"Hugo J.","family":"Bellen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2007,4,18]]},"references-count":47,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2007,4,18]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0000375","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,4,18]]}}}