{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T03:39:42Z","timestamp":1789270782520,"version":"build-2803163510"},"reference-count":74,"publisher":"Oxford University Press (OUP)","issue":"24","license":[{"start":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T00:00:00Z","timestamp":1626652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 HL 134599"],"award-info":[{"award-number":["P01 HL 134599"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Indiana University School of Medicine Strategic Research Initiative"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,30]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Loss of function of ZIC3 causes heterotaxy (OMIM #306955), a disorder characterized by organ laterality defects including complex heart defects. Studies using Zic3 mutant mice have demonstrated that loss of Zic3 causes heterotaxy due to defects in establishment of left\u2013right (LR) signaling, but the mechanistic basis for these defects remains unknown. Here, we demonstrate Zic3 null mice undergo cilia positioning defects at the embryonic node consistent with impaired planar cell polarity (PCP). Cell-based assays demonstrate that ZIC3 must enter the nucleus to regulate PCP and identify multiple critical ZIC3 domains required for regulation of PCP signaling. Furthermore, we show that Zic3 displays a genetic interaction with the PCP membrane protein Vangl2 and the PCP effector genes Rac1 and Daam1 resulting in increased frequency and severity of neural tube and heart defects. Gene and protein expression analyses indicate that Zic3 null embryos display disrupted expression of PCP components and reduced phosphorylation of the core PCP protein DVL2 at the time of LR axis determination. These results demonstrate that ZIC3 interacts with PCP signaling during early development, identifying a novel role for this transcription factor, and adding additional evidence about the importance of PCP function for normal LR patterning and subsequent heart development.<\/jats:p>","DOI":"10.1093\/hmg\/ddab195","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T11:10:27Z","timestamp":1626347427000},"page":"2402-2415","source":"Crossref","is-referenced-by-count":24,"title":["Loss of<i>Zic3<\/i>impairs planar cell polarity leading to abnormal left\u2013right signaling, heart defects and neural tube defects"],"prefix":"10.1093","volume":"30","author":[{"given":"Helen M","family":"Bellchambers","sequence":"first","affiliation":[{"name":"Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie M","family":"Ware","sequence":"additional","affiliation":[{"name":"Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,7,19]]},"reference":[{"key":"2021120506364945000_ref1","first-page":"e38","article-title":"Heart disease and stroke Statistics-2016 update: a report from the American Heart Association","volume":"133","author":"Mozaffarian","year":"2016","journal-title":"Circulation"},{"key":"2021120506364945000_ref2","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/ajmg.c.30228","article-title":"Disorders of left-right asymmetry: heterotaxy and situs inversus","volume":"151c","author":"Sutherland","year":"2009","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"2021120506364945000_ref3","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1101\/gad.268979.115","article-title":"Lhx1 functions together with Otx2, Foxa2, and Ldb1 to govern anterior mesendoderm, node, and midline development","volume":"29","author":"Costello","year":"2015","journal-title":"Genes Dev."},{"key":"2021120506364945000_ref4","doi-asserted-by":"crossref","first-page":"15765","DOI":"10.1073\/pnas.0704344104","article-title":"The mouse homeobox gene Noto regulates node morphogenesis, notochordal ciliogenesis, and left right patterning","volume":"104","author":"Beckers","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021120506364945000_ref5","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1172\/JCI4786","article-title":"Mutation of the mouse hepatocyte nuclear factor\/forkhead homologue 4 gene results in an absence of cilia and random left-right asymmetry","volume":"102","author":"Chen","year":"1998","journal-title":"J. Clin. Invest."},{"key":"2021120506364945000_ref6","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1086\/380998","article-title":"Identification and functional analysis of ZIC3 mutations in heterotaxy and related congenital heart defects","volume":"74","author":"Ware","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"2021120506364945000_ref7","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.ydbio.2012.01.011","article-title":"An essential and highly conserved role for Zic3 in left-right patterning, gastrulation and convergent extension morphogenesis","volume":"364","author":"Cast","year":"2012","journal-title":"Dev. Biol."},{"key":"2021120506364945000_ref8","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1242\/dev.129.9.2293","article-title":"A complex syndrome of left-right axis, central nervous system and axial skeleton defects in Zic3 mutant mice","volume":"129","author":"Purandare","year":"2002","journal-title":"Development"},{"key":"2021120506364945000_ref9","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.ydbio.2011.10.026","article-title":"Xenopus Zic3 controls notochord and organizer development through suppression of the Wnt\/beta-catenin signaling pathway","volume":"361","author":"Fujimi","year":"2012","journal-title":"Dev. Biol."},{"key":"2021120506364945000_ref10","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1093\/hmg\/dds002","article-title":"Preaxial polydactyly caused by Gli3 haploinsufficiency is rescued by Zic3 loss of function in mice","volume":"21","author":"Quinn","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"2021120506364945000_ref11","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1002\/dvdy.20719","article-title":"Heart defects in X-linked heterotaxy: evidence for a genetic interaction of Zic3 with the nodal signaling pathway","volume":"235","author":"Ware","year":"2006","journal-title":"Dev. Dyn."},{"key":"2021120506364945000_ref12","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/978-981-10-7311-3_15","article-title":"ZIC3 in Heterotaxy","volume":"1046","author":"Bellchambers","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"2021120506364945000_ref13","doi-asserted-by":"crossref","first-page":"e268","DOI":"10.1371\/journal.pbio.0030268","article-title":"De novo formation of left-right asymmetry by posterior tilt of nodal cilia","volume":"3","author":"Nonaka","year":"2005","journal-title":"PLoS Biol."},{"key":"2021120506364945000_ref14","doi-asserted-by":"crossref","first-page":"e8999","DOI":"10.1371\/journal.pone.0008999","article-title":"Planar cell polarity enables posterior localization of nodal cilia and left-right axis determination during mouse and Xenopus embryogenesis","volume":"5","author":"Antic","year":"2010","journal-title":"PLoS One"},{"key":"2021120506364945000_ref15","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/ncb2020","article-title":"Planar polarization of node cells determines the rotational axis of node cilia","volume":"12","author":"Hashimoto","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"2021120506364945000_ref16","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/nature09129","article-title":"Planar cell polarity breaks bilateral symmetry by controlling ciliary positioning","volume":"466","author":"Song","year":"2010","journal-title":"Nature"},{"key":"2021120506364945000_ref17","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1242\/dev.122804","article-title":"Planar cell polarity in moving cells: think globally, act locally","volume":"144","author":"Davey","year":"2017","journal-title":"Development"},{"key":"2021120506364945000_ref18","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1242\/bio.015750","article-title":"Prickle1 mutation causes planar cell polarity and directional cell migration defects associated with cardiac outflow tract anomalies and other structural birth defects","volume":"5","author":"Gibbs","year":"2016","journal-title":"Biol. Open."},{"key":"2021120506364945000_ref19","first-page":"1153","article-title":"Genetic interactions between planar cell polarity genes cause diverse neural tube defects in mice","volume":"7","author":"Murdoch","year":"2014","journal-title":"Dis. Model. Mech."},{"key":"2021120506364945000_ref20","doi-asserted-by":"crossref","first-page":"3707","DOI":"10.1242\/dev.052001","article-title":"Frizzled 1 and frizzled 2 genes function in palate, ventricular septum and neural tube closure: general implications for tissue fusion processes","volume":"137","author":"Yu","year":"2010","journal-title":"Development"},{"key":"2021120506364945000_ref21","article-title":"Planar cell polarity signaling regulates polarized second heart field morphogenesis to promote both arterial and venous pole septation","volume":"146","author":"Li","year":"2019","journal-title":"Development"},{"key":"2021120506364945000_ref22","doi-asserted-by":"crossref","first-page":"589414","DOI":"10.1155\/2011\/589414","article-title":"Planar cell polarity signaling pathway in congenital heart diseases","volume":"2011","author":"Wu","year":"2011","journal-title":"J. Biomed. Biotechnol."},{"key":"2021120506364945000_ref23","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1002\/bies.20526","article-title":"Planar cell polarity signaling in vertebrates","volume":"29","author":"Jones","year":"2007","journal-title":"BioEssays"},{"key":"2021120506364945000_ref24","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.devcel.2009.11.014","article-title":"Local protease signaling contributes to neural tube closure in the mouse embryo","volume":"18","author":"Camerer","year":"2010","journal-title":"Dev. Cell"},{"key":"2021120506364945000_ref25","doi-asserted-by":"crossref","first-page":"e13273","DOI":"10.7554\/eLife.13273","article-title":"Regulation of cell protrusions by small GTPases during fusion of the neural folds","volume":"5","author":"Rolo","year":"2016","journal-title":"eLife"},{"key":"2021120506364945000_ref26","doi-asserted-by":"crossref","first-page":"e0232025","DOI":"10.1371\/journal.pone.0232025","article-title":"Placental defects lead to embryonic lethality in mice lacking the Formin and PCP proteins Daam1 and Daam2","volume":"15","author":"Nakaya","year":"2020","journal-title":"PLoS One"},{"key":"2021120506364945000_ref27","doi-asserted-by":"crossref","first-page":"15859","DOI":"10.1523\/JNEUROSCI.3998-09.2009","article-title":"The small GTPase Rac1 regulates auditory hair cell morphogenesis","volume":"29","author":"Grimsley-Myers","year":"2009","journal-title":"J. Neurosci."},{"key":"2021120506364945000_ref28","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.ydbio.2015.10.003","article-title":"DAAM1 and DAAM2 are co-required for myocardial maturation and sarcomere assembly","volume":"408","author":"Ajima","year":"2015","journal-title":"Dev. Biol."},{"key":"2021120506364945000_ref29","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.devcel.2017.02.010","article-title":"A Wnt5 activity asymmetry and intercellular signaling via PCP proteins polarize node cells for left-right symmetry breaking","volume":"40","author":"Minegishi","year":"2017","journal-title":"Dev. Cell"},{"key":"2021120506364945000_ref30","doi-asserted-by":"crossref","first-page":"e1003852","DOI":"10.1371\/journal.pgen.1003852","article-title":"Genome wide analysis reveals Zic3 interaction with distal regulatory elements of stage specific developmental genes in zebrafish","volume":"9","author":"Winata","year":"2013","journal-title":"PLoS Genet."},{"key":"2021120506364945000_ref31","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1093\/hmg\/ddt001","article-title":"Zic3 is required in the migrating primitive streak for node morphogenesis and left-right patterning","volume":"22","author":"Sutherland","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"2021120506364945000_ref32","doi-asserted-by":"crossref","first-page":"3011","DOI":"10.1242\/dev.059766","article-title":"Rac1 mediates morphogenetic responses to intercellular signals in the gastrulating mouse embryo","volume":"138","author":"Migeotte","year":"2011","journal-title":"Development"},{"key":"2021120506364945000_ref33","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.cell.2005.04.008","article-title":"Mechanism of nodal flow: a conserved symmetry breaking event in left-right axis determination","volume":"121","author":"Okada","year":"2005","journal-title":"Cell"},{"key":"2021120506364945000_ref34","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1093\/hmg\/ddt558","article-title":"Novel mutations in Lrp6 orthologs in mouse and human neural tube defects affect a highly dosage-sensitive Wnt non-canonical planar cell polarity pathway","volume":"23","author":"Allache","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"2021120506364945000_ref35","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1002\/bdra.23273","article-title":"Genetic studies of ANKRD6 as a molecular switch between Wnt signaling pathways in human neural tube defects","volume":"103","author":"Allache","year":"2015","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"2021120506364945000_ref36","doi-asserted-by":"crossref","first-page":"4832","DOI":"10.1038\/ncomms5832","article-title":"The ubiquitin ligase PDZRN3 is required for vascular morphogenesis through Wnt\/planar cell polarity signalling","volume":"5","author":"Sewduth","year":"2014","journal-title":"Nat. Commun."},{"key":"2021120506364945000_ref37","doi-asserted-by":"crossref","first-page":"e0191864","DOI":"10.1371\/journal.pone.0191864","article-title":"Functional analysis of the C. elegans cyld-1 gene reveals extensive similarity with its human homolog","volume":"13","author":"Hadweh","year":"2018","journal-title":"PLoS One"},{"key":"2021120506364945000_ref38","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1016\/j.bbamcr.2011.08.005","article-title":"Zac1 functional interactions mediate AP-1 transcriptional activity","volume":"1813","author":"Wang","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"2021120506364945000_ref39","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/hmg\/ddl461","article-title":"Nuclear import and export signals are essential for proper cellular trafficking and function of ZIC3","volume":"16","author":"Bedard","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"2021120506364945000_ref40","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1002\/stem.527","article-title":"The pluripotency regulator Zic3 is a direct activator of the Nanog promoter in ESCs","volume":"28","author":"Lim","year":"2010","journal-title":"Stem Cells"},{"key":"2021120506364945000_ref41","doi-asserted-by":"crossref","first-page":"6889","DOI":"10.1074\/jbc.C000773200","article-title":"Physical and functional interactions between Zic and Gli proteins","volume":"276","author":"Koyabu","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2021120506364945000_ref42","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.bbrc.2004.05.158","article-title":"Myogenic repressor I-mfa interferes with the function of Zic family proteins","volume":"320","author":"Mizugishi","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021120506364945000_ref43","doi-asserted-by":"crossref","first-page":"4929","DOI":"10.1128\/MCB.22.13.4929-4942.2002","article-title":"The Bax subfamily of Bcl2-related proteins is essential for apoptotic signal transduction by c-Jun NH(2)-terminal kinase","volume":"22","author":"Lei","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"2021120506364945000_ref44","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/pr.2013.147","article-title":"Heterotaxy-spectrum heart defects in Zic3 hypomorphic mice","volume":"74","author":"Haaning","year":"2013","journal-title":"Pediatr. Res."},{"key":"2021120506364945000_ref45","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1093\/hmg\/10.22.2593","article-title":"Severe neural tube defects in the loop-tail mouse result from mutation of Lpp1, a novel gene involved in floor plate specification","volume":"10","author":"Murdoch","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"2021120506364945000_ref46","doi-asserted-by":"crossref","first-page":"14001","DOI":"10.1523\/JNEUROSCI.1307-13.2013","article-title":"Postnatal refinement of auditory hair cell planar polarity deficits occurs in the absence of Vangl2","volume":"33","author":"Copley","year":"2013","journal-title":"J. Neurosci."},{"key":"2021120506364945000_ref47","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1203\/PDR.0b013e3181ee0028","article-title":"A mouse model of conduction system patterning abnormalities in heterotaxy syndrome","volume":"68","author":"Czosek","year":"2010","journal-title":"Pediatr. Res."},{"key":"2021120506364945000_ref48","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1242\/dev.055566","article-title":"Dishevelled-associated activator of morphogenesis 1 (Daam1) is required for heart morphogenesis","volume":"138","author":"Li","year":"2011","journal-title":"Development"},{"key":"2021120506364945000_ref49","doi-asserted-by":"crossref","first-page":"4044","DOI":"10.1073\/pnas.1200421109","article-title":"Wnt5a-Ror-dishevelled signaling constitutes a core developmental pathway that controls tissue morphogenesis","volume":"109","author":"Ho","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021120506364945000_ref50","doi-asserted-by":"crossref","first-page":"3104","DOI":"10.1038\/emboj.2012.144","article-title":"Identification of a novel Wnt5a-CK1\u025b-Dvl2-Plk1-mediated primary cilia disassembly pathway","volume":"31","author":"Lee","year":"2012","journal-title":"EMBO J."},{"key":"2021120506364945000_ref51","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1002\/dvdy.20668","article-title":"Zic3 is critical for early embryonic patterning during gastrulation","volume":"235","author":"Ware","year":"2006","journal-title":"Dev. Dyn."},{"key":"2021120506364945000_ref52","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1093\/hmg\/dds494","article-title":"Zic3 is required in the extra-cardiac perinodal region of the lateral plate mesoderm for left-right patterning and heart development","volume":"22","author":"Jiang","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"2021120506364945000_ref53","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1126\/science.285.5426.403","article-title":"Differences in left-right axis pathways in mouse and chick: functions of FGF8 and SHH","volume":"285","author":"Meyers","year":"1999","journal-title":"Science"},{"key":"2021120506364945000_ref54","doi-asserted-by":"crossref","first-page":"11376","DOI":"10.1073\/pnas.96.20.11376","article-title":"Multiple left-right asymmetry defects in Shh(\u2212\/\u2212) mutant mice unveil a convergence of the shh and retinoic acid pathways in the control of Lefty-1","volume":"96","author":"Tsukui","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2021120506364945000_ref55","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/S0092-8674(01)00385-3","article-title":"Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L\/R asymmetry by the mouse node","volume":"105","author":"Zhang","year":"2001","journal-title":"Cell"},{"key":"2021120506364945000_ref56","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.ydbio.2013.05.011","article-title":"Wnt signaling regulates left-right axis formation in the node of mouse embryos","volume":"380","author":"Kitajima","year":"2013","journal-title":"Dev. Biol."},{"key":"2021120506364945000_ref57","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1038\/ncomms2319","article-title":"Fluid flow and interlinked feedback loops establish left-right asymmetric decay of Cerl2 mRNA","volume":"3","author":"Nakamura","year":"2012","journal-title":"Nat. Commun."},{"key":"2021120506364945000_ref58","doi-asserted-by":"crossref","first-page":"5425","DOI":"10.1242\/dev.02149","article-title":"Wnt3a links left-right determination with segmentation and anteroposterior axis elongation","volume":"132","author":"Nakaya","year":"2005","journal-title":"Development"},{"key":"2021120506364945000_ref59","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.ydbio.2012.07.023","article-title":"Disheveled mediated planar cell polarity signaling is required in the second heart field lineage for outflow tract morphogenesis","volume":"370","author":"Sinha","year":"2012","journal-title":"Dev. Biol."},{"key":"2021120506364945000_ref60","doi-asserted-by":"crossref","first-page":"29","DOI":"10.3390\/jcdd8030029","article-title":"Myocardium-specific deletion of Rac1 causes ventricular noncompaction and outflow tract defects","volume":"8","author":"Leung","year":"2021","journal-title":"J. Cardiovasc. Dev. Dis."},{"key":"2021120506364945000_ref61","doi-asserted-by":"crossref","first-page":"e1004871","DOI":"10.1371\/journal.pgen.1004871","article-title":"Vangl2-regulated polarisation of second heart field-derived cells is required for outflow tract lengthening during cardiac development","volume":"10","author":"Ramsbottom","year":"2014","journal-title":"PLoS Genet."},{"key":"2021120506364945000_ref62","doi-asserted-by":"crossref","first-page":"3459","DOI":"10.1093\/hmg\/ddn239","article-title":"Functional and structural basis of the nuclear localization signal in the ZIC3 zinc finger domain","volume":"17","author":"Hatayama","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"2021120506364945000_ref63","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1002\/humu.22457","article-title":"Genetic and functional analyses of ZIC3 variants in congenital heart disease","volume":"35","author":"Cowan","year":"2014","journal-title":"Hum. Mutat."},{"key":"2021120506364945000_ref64","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1038\/ejhg.2016.91","article-title":"Rare novel variants in the ZIC3 gene cause X-linked heterotaxy","volume":"24","author":"Paulussen","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"2021120506364945000_ref65","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.bbrc.2009.07.012","article-title":"The planar cell polarity (PCP) protein Diversin translocates to the nucleus to interact with the transcription factor AF9","volume":"387","author":"Haribaskar","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021120506364945000_ref66","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ydbio.2012.01.025","article-title":"Nuclear localization of Prickle2 is required to establish cell polarity during early mouse embryogenesis","volume":"364","author":"Tao","year":"2012","journal-title":"Dev. Biol."},{"key":"2021120506364945000_ref67","doi-asserted-by":"crossref","first-page":"44197","DOI":"10.1074\/jbc.M404977200","article-title":"The Rac1 C-terminal polybasic region regulates the nuclear localization and protein degradation of Rac1","volume":"279","author":"Lanning","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2021120506364945000_ref68","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.devcel.2014.12.019","article-title":"Rac1 nucleocytoplasmic shuttling drives nuclear shape changes and tumor invasion","volume":"32","author":"Navarro-L\u00e9rida","year":"2015","journal-title":"Dev. Cell"},{"key":"2021120506364945000_ref69","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/jbiol20","article-title":"Nuclear localization is required for dishevelled function in Wnt\/\u03b2-catenin signaling","volume":"4","author":"Itoh","year":"2005","journal-title":"J. Biol."},{"key":"2021120506364945000_ref70","doi-asserted-by":"crossref","first-page":"8260","DOI":"10.1038\/sj.onc.1208007","article-title":"Cross-talk between Rac1 GTPase and dysregulated Wnt signaling pathway leads to cellular redistribution of beta-catenin and TCF\/LEF-mediated transcriptional activation","volume":"23","author":"Esufali","year":"2004","journal-title":"Oncogene"},{"key":"2021120506364945000_ref71","doi-asserted-by":"crossref","first-page":"3933","DOI":"10.1242\/jcs.167742","article-title":"Rac1 augments Wnt signaling by stimulating \u03b2-catenin-lymphoid enhancer factor-1 complex assembly independent of \u03b2-catenin nuclear import","volume":"128","author":"Jamieson","year":"2015","journal-title":"J. Cell Sci."},{"key":"2021120506364945000_ref72","doi-asserted-by":"crossref","first-page":"9428","DOI":"10.1074\/jbc.M112.448480","article-title":"Functional consequences of Wnt-induced dishevelled 2 phosphorylation in canonical and noncanonical Wnt signaling","volume":"288","author":"Gonz\u00e1lez-Sancho","year":"2013","journal-title":"J. Biol. Chem."},{"key":"2021120506364945000_ref73","doi-asserted-by":"crossref","first-page":"5652","DOI":"10.4049\/jimmunol.170.11.5652","article-title":"Rac1 deletion in mouse neutrophils has selective effects on neutrophil functions","volume":"170","author":"Glogauer","year":"2003","journal-title":"J. Immunol."},{"key":"2021120506364945000_ref74","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/hmg\/advance-article-pdf\/doi\/10.1093\/hmg\/ddab195\/39568786\/ddab195.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/30\/24\/2402\/41389776\/ddab195.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/30\/24\/2402\/41389776\/ddab195.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T06:12:47Z","timestamp":1725430367000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/30\/24\/2402\/6323447"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,19]]},"references-count":74,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2021,7,19]]},"published-print":{"date-parts":[[2021,11,30]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddab195","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,12,15]]},"published":{"date-parts":[[2021,7,19]]}}}