Skip to main content

Advertisement

SpringerLink
Log in

Overexpressed Down Syndrome Cell Adhesion Molecule (DSCAM) Deregulates P21-Activated Kinase (PAK) Activity in an In Vitro Neuronal Model of Down Syndrome: Consequences on Cell Process Formation and Extension

  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

In humans, Down syndrome (DS) is caused by the presence of an extra copy of autosome 21. The most striking finding in DS patients is intellectual disability and the onset of Alzheimer’s disease (AD)-like neuropathology in adulthood. Gene overdose is most likely to underlie both developmental impairments, as well as altered neuronal function in DS. Lately, the disruption of cellular signaling and regulatory pathways has been implicated in DS pathophysiology, and many of such pathways may represent common targets for diverse DS-related genes, which could in turn represent attractive therapeutical targets. In this regard, one DS-related gene Down Syndrome Cell Adhesion Molecule (DSCAM), has important functions in neuronal proliferation, maturation, and synaptogenesis. p21-associated kinases (PAKs) appear as a most interesting possibility for study, as DSCAM is known to regulate the PAKs pathway. Hence, in DS, overexpressed DSCAM could deregulate PAKs activity and affect signaling pathways that regulate synaptic plasticity such as dendritic spine dynamics and axon guidance and growth. In the present work, we used an immortalized cell line derived from the cerebral cortex of an animal model of DS such as the trisomy 16 (Ts16) fetal mouse (named CTb), and a similar cell line established from a normal littermate (named CNh), to study the effect of DSCAM in the PAKs pathway. The present study shows that DSCAM is overexpressed in CTb cells by approximately twofold, compared to CNh cells. Congruently, PAK1, as well as its downstream effectors LIMK and cofilin, stay phosphorylated for longer periods after DSCAM activation in the CTb cells, leading to an altered actin dynamics, expressed as an increased basal F/G ratio and reduced neurite growth, in the trisomic condition. The present work presents the correlation between DSCAM gene overexpression and a dysregulation of the PAK pathway, resulting in altered morphological parameters of neuronal plasticity in the trisomic cell line, namely decreased number and length of processes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Acuña M, Pérez-Nuñez R, Noriega J, Cárdenas AM, Bacigalupo J, Delgado R, Arriagada C, Segura-Aguilar J, Caviedes R, Caviedes P (2012) Altered voltage dependent calcium currents in a neuronal cell line derived from the cerebral cortex of a trisomy 16 fetal mouse, an animal model of Down syndrome. Neurotox Res 22(1):59–68

    Article  PubMed  Google Scholar 

  • Allen D, Martín J, Arriagada C, Cárdenas AM, Rapoport SI, Caviedes R, Caviedes P (2000) Impaired cholinergic function in cell lines derived from the cerebral cortex of normal and trisomy 16 mice. Eur J Neurosci 12(9):3259–3264

    Article  CAS  PubMed  Google Scholar 

  • Arber S, Barbayannis FA, Hanser H, Schneider C, Stanyon CA, Bernard O, Caroni P (1998) Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase. Nature 393(6687):805–809

    Article  CAS  PubMed  Google Scholar 

  • Arias-Romero LE, Chernoff J (2008) A tale of two Paks. Biol Cell 100(2):97–108

    Article  CAS  PubMed  Google Scholar 

  • Arron JR, Winslow MM, Polleri A, Chang CP, Wu H, Gao X, Neilson JR, Chen L, Heit JJ, Kim SK, Yamasaki N, Miyakawa T, Francke U, Graef IA, Crabtree GR (2006) NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21. Nature 7093:595–600

    Article  Google Scholar 

  • Ault B, Caviedes P, Rapoport SI (1989) Neurophysiological abnormalities in cultured dorsal root ganglion neurons from the trisomy 16 mouse fetus, a model for Down Syndrome. Brain Res 485:165–170

    Article  CAS  PubMed  Google Scholar 

  • Bagrodia S, Dérijard B, Davis RJ, Cerione RA (1995) Cdc42 and PAK-mediated signaling leads to Jun kinase and p38 mitogen-activated protein kinase activation. J Biol Chem 270(47):27995–27998

    Article  CAS  PubMed  Google Scholar 

  • Bahn S, Mimmack M, Ryan M, Caldwell MA, Jauniaux E, Starkey M, Svendsen CN, Emson P (2002) Neuronal target genes of the neuron-restrictive silencer factor in neurospheres derived from fetuses with Down’s syndrome: a gene expression study. Lancet 359(9303):310–315

    Article  CAS  PubMed  Google Scholar 

  • Belichenko NP, Belichenko PV, Kleschevnikov AM, Salehi A, Reeves RH, Mobley WC (2009) The “Down syndrome critical region” is sufficient in the mouse model to confer behavioral, neurophysiological, and synaptic phenotypes characteristic of Down syndrome. J Neurosci 29(18):5938–5948

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bokoch GM (2003) Biology of the p21-activated kinases. Annu Rev Biochem 72:743–781

    Article  CAS  PubMed  Google Scholar 

  • Cárdenas AM, Rodríguez MP, Cortés MP, Alvarez RM, Wei W, Rapoport SI, Shimahara T, Caviedes R, Caviedes P (1999) Intracellular calcium signals in immortal cell lines derived from the cerebral cortex of normal and trisomy 16 fetal mice, an animal model of human trisomy 21 (Down syndrome). NeuroReport 10(2):363–369

    Article  PubMed  Google Scholar 

  • Caviedes P, Ault B, Rapoport SI (1990) The role of altered sodium currents in the action potential abnormalities of cultured dorsal root ganglion neurons from trisomy 21 (Down syndrome) human fetuses. Brain Res 510:229–236

    Article  CAS  PubMed  Google Scholar 

  • Caviedes P, Caviedes R, Rapoport SI (2006) Altered calcium currents in cultured sensory neurons of normal and trisomy 16 mouse fetuses, an animal model for human trisomy 21 (Down syndrome). Biol Res 39:471–481

    Article  CAS  PubMed  Google Scholar 

  • Chen BE, Kondo M, Garnier A, Watson FL, Püettmann-Holgado R, Lamar DR, Schmucker D (2006) The molecular diversity of Dscam is functionally required for neuronal wiring specificity in Drosophila. Cell 125(3):607-620

    Article  CAS  PubMed  Google Scholar 

  • Chong C, Tan L, Lim L, Manser E (2001) The mechanism of PAK activation. Autophosphorylation events in both regulatory and kinase domains control activity. J Biol Chem 276(20):17347–17353

    Article  CAS  PubMed  Google Scholar 

  • Cook M, Bolkan BJ, Kretzschmar D (2014) Increased actin polymerization and stabilization interferes with neuronal function and survival in the AMPKγ mutant Loechrig. PLoS One 9(2):E89847

    Article  PubMed  PubMed Central  Google Scholar 

  • Delabar JM, Theophile D, Rahmani Z, Chettouh Z, Blouin JL, Prieur M, Noel B, Sinet PM (1993) Molecular mapping of twenty-four features of Down syndrome on chromosome 21. Eur J Hum Genet 1:114–124

    CAS  PubMed  Google Scholar 

  • Dubos A, Combeau G, Bernardinelli Y, Barnier JV, Hartley O, Gaertner H, Boda B, Muller D (2012) Alteration of synaptic network dynamics by the intellectual disability protein PAK3. J Neurosci 32:519–527

    Article  CAS  PubMed  Google Scholar 

  • Epstein CJ (1986a) The neurobiology of Down syndrome. Raven Press, New York, pp 1–15

    Google Scholar 

  • Epstein CJ (1986b) The consequence of chromosomal imbalance: principles, mechanisms, models. Cambridge University Press, New York

    Book  Google Scholar 

  • Epstein CJ (2006) Down’s syndrome: critical genes in a critical region. Nature 441(7093):582–583

    Article  CAS  PubMed  Google Scholar 

  • Epstein CJ, Korenberg JR, Anneren G, Antonarakis SE, Ayme S, Courchesne E, Epstein LB, Fowler A, Groner Y, Huret JL (1991) Protocols to establish genotype–phenotype correlations in Down syndrome. Am J Hum Genet 49:207–235

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fiedler J, Rapoport SI, Epstein CJ, Caviedes R, Caviedes P (1994) Altered cholinergic function in cultured neurons from the trisomy 16 mouse fetus, a model for Down Syndrome. Brain Res 658:27–32

    Article  CAS  PubMed  Google Scholar 

  • Fuerst PG, Koizumi A, Masland RH, Burgess RW (2008) Neurite arborization and mosaic spacing in the mouse retina require DSCAM. Nature 451(7177):470–474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fulga TA, Elson-Schwab I, Khurana V, Steinhilb ML, Spires TL, Hyman BT, Feany MB (2007) Abnormal bundling and accumulation of F-actin mediates tau-induced neuronal degeneration in vivo. Nat Cell Biol 9(2):139–148

    Article  CAS  PubMed  Google Scholar 

  • Galdzicki Z, Coan EJ, Rapoport SI, Stoll J (1998) Increased expression of voltage-activated calcium channels in cultured hippocampal neurons from mouse trisomy 16, a model for Down syndrome. Brain Res Mol Brain Res 56(1–2):200–206

    Article  CAS  PubMed  Google Scholar 

  • Gardiner KJ (2014) Pharmacological approaches to improving cognitive function in Down syndrome: current status and considerations. Drug Des Devel Ther 9:103–125

    Article  PubMed  PubMed Central  Google Scholar 

  • Golden JA, Hyman BT (1994) Development of the superior temporal neocortex is anomalous in trisomy 21. J Neuropathol Exp Neurol 53(5):513–520

    Article  CAS  PubMed  Google Scholar 

  • Gwack Y, Sharma S, Nardone J, Tanasa B, Iuga A, Srikanth S, Okamura H, Bolton D, Feske S, Hogan PG, Rao A (2006) A genome-wide Drosophila RNAi screen identifies DYRK-family kinases as regulators of NFAT. Nature 441(7093):646–650

    Article  CAS  PubMed  Google Scholar 

  • Hattori M, Fujiyama A, Taylor TD, Watanabe H (2000) The DNA sequence of human chromosome 21. Nature 405(18):311–319

    CAS  PubMed  Google Scholar 

  • Hattori D, Millard SS, Wojtowicz WM, Zipursky SL (2008) Dscam-mediated cell recognition regulates neural circuit formation. Annu Rev Cell Dev Biol 24(1):597–620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Head E, Lott IT, Wilcock DM, Lemere CA (2016) Aging in Down Syndrome and the development of Alzheimer’s disease neuropathology. Curr Alzheimer Res 3(1):18–29

    Google Scholar 

  • Huang H, Shao Q, Qu C, Yang T, Dwyer T, Liu G (2015) Coordinated interaction of Down syndrome cell adhesion molecule and deleted in colorectal cancer with dynamic TUBB3 mediates Netrin-1-induced axon branching. Neuroscience 293:109–122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jang S, Cho HH, Cho YB, Park JS, Jeong HS (2010) Functional neural differentiation of human adipose tissue-derived stem cells using bFGF and forskolin. BMC Cell Biol 11:25

    Article  PubMed  PubMed Central  Google Scholar 

  • Jia YL, Jing LJ, Li JY, Lu JJ, Han R, Wang SY, Peng T, Jia YJ (2011) Expression and significance of DSCAM in the cerebral cortex of APP transgenic mice. Neurosci Lett 491:153–157

    Article  CAS  PubMed  Google Scholar 

  • Jiang X, Liu C, Yu T, Zhang L, Meng K, Xing Z, Belichenko PV, Kleschevnikov AM, Pao A, Peresie J, Wie S, Mobley WC, Yu YE (2015) Genetic dissection of the Down syndrome critical region. Hum Mol Genet 24(22):6540–6551

    Article  CAS  PubMed  Google Scholar 

  • Keino-Masu K, Masu M, Hinck L, Leonardo ED, Chan SS, Culotti JG, Tessier-Lavigne M (1996) Deleted in colorectal cancer (DCC) encodes a netrin receptor. Cell 87(2):175–185

    Article  CAS  PubMed  Google Scholar 

  • Kreis P, Barnier JV (2009) PAK signalling in neuronal physiology. Cell Signal 21(3):384–393

    Article  CAS  PubMed  Google Scholar 

  • Kreis P, Thévenot E, Rousseau V, Boda B, Muller D, Barnier JV (2007) The p21-activated kinase 3 implicated in mental retardation regulates spine morphogenesis through a Cdc42-dependent pathway. J Biol Chem 282(29):21497–21506

    Article  CAS  PubMed  Google Scholar 

  • Liu G, Li W, Wang L, Kar A, Guan KL, Rao Y, Wu JY (2009) DSCAM functions as a netrin receptor in commissural axon pathfinding. Proc Natl Acad Sci USA 106(8):2951–2956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma QL, Yang F, Calon F, Ubeda OJ, Hansen JE, Weisbart RH, Beech W, Frautschy SA, Cole GM (2008) p21-activated kinase-aberrant activation and translocation in Alzheimer disease pathogenesis. J Biol Chem 283(20):14132–14143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marin-Padilla M (1972) Structural abnormalities of the cerebral cortex in human chromosomal aberrations: a Golgi study. Brain Res 44:625–629

    Article  CAS  PubMed  Google Scholar 

  • Marin-Padilla M (1976) Pyramidal cell abnormalities in the motor cortex of a child with Down’s syndrome: a Golgi study. J Comp Neurol 167:63–81

    Article  CAS  PubMed  Google Scholar 

  • Millard SS, Zipursky SL (2008) DSCAM-mediated repulsion controls tiling and selfavoidance. Curr Opin Neurobiol 18:84–89

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Montesinos ML (2014) Roles for DSCAM and DSCAML1 in central nervous system development and disease. Adv Neurobiol 8:249–270

    Article  PubMed  Google Scholar 

  • Nelson PG, Fitzgerald S, Rapoport SI, Neale EA, Galdzicki Z, Dunlap V, Bowers L, Agoston D (1997) Cerebral cortical astroglia from the trisomy 16 mouse, a model for down syndrome, produce neuronal cholinergic deficits in cell culture. Proc Natl Acad Sci USA 94(23):12644–12648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nguyen TV, Galvan V, Huang W, Banwait S, Tang H, Zhang J, Bredesen DE (2008) Signal transduction in Alzheimer disease: p21-activated kinase signaling requires C-terminal cleavage of APP at Asp664. J Neurochem 104(4):1065–1080

    Article  CAS  PubMed  Google Scholar 

  • Nieminen K, Suárez-Isla B, Rapoport SI (1988) Electrical properties of cultured dorsal root ganglion neurons from normal and trisomy 21 human fetal tissue. Brain Res 474:246–254

    Article  CAS  PubMed  Google Scholar 

  • Nölle A, Zeug A, van Bergeijk J, Tönges L, Gerhard R, Brinkmann H, Al Rayes S, Hensel N, Schill Y, Apkhazava D, Jablonka S, O’mer J, Srivastav R, Baasner A, Lingor P, Wirth B, Ponimaskin E, Niedenthal R, Grothe C, Claus P (2011) The spinal muscular atrophy disease protein SMN is linked to the rho-kinase pathway via profiling. Hum Mol Genet 20(24):4865–4878

    Article  PubMed  Google Scholar 

  • Olson LE, Richtsmeier JT, Leszl J, Reeves RH (2004) A chromosome 21 critical region does not cause specific Down syndrome phenotypes. Science 306(5696):687–690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Opazo P, Saud K, de Saint Pierre M, Cárdenas AM, Allen DD, Segura-Aguilar J, Caviedes R, Caviedes P (2006) Knockdown of amyloid precursor protein normalizes cholinergic function in a cell line derived from the cerebral cortex of a trisomy 16 mouse, an animal model of Down syndrome. J Neurosci Res 84:1303–1310

    Article  CAS  PubMed  Google Scholar 

  • Orozco CB, Epstein CJ, Rapoport SI (1988) Voltage-activated sodium conductances in cultured normal and trisomy 16 dorsal root ganglion neurons from the fetal mouse. Brain Res 466:265–274

    Article  CAS  PubMed  Google Scholar 

  • Oster-Granite ML (1986) The neurobiologic consequences of autosomal trisomy in mice and men. Brain Res Bull 16:767–771

    Article  CAS  PubMed  Google Scholar 

  • Palmesino E, Haddick PC, Tessier-Lavigne M, Kania A (2012) Genetic analysis of DSCAM’s role as a Netrin-1 receptor in vertebrates. J Neurosci 32(2):411–416

    Article  CAS  PubMed  Google Scholar 

  • Pozueta J, Lefort R, Shelanski ML (2013) Synaptic changes in Alzheimer’s disease and its models. Neuroscience 251:51–65

    Article  CAS  PubMed  Google Scholar 

  • Pulsifer MB (1996) The neuropsychology of mental retardation. J Int Neuropsychol Soc 2:159–176

    Article  CAS  PubMed  Google Scholar 

  • Purohit A, Li W, Qu Ch, Dwyer T, Shao Q, Guan K, Liu G (2012) Down syndrome cell adhesion molecule (DSCAM) associates with uncoordinated-5C (UNC5C) in netrin-1-mediated growth cone collapse. J Biol Chem 287:27126–27138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Purpura DP (1974) Dendritic spine ‘dysgenesis’ and mental retardation. Science 186:1126–1128

    Article  CAS  PubMed  Google Scholar 

  • Qu Ch, Li W, Shao Q, Dwyer T, Huang H, Yang T, Liu G (2013) c-Jun N-terminal kinase 1 (JNK1) is required for coordination of netrin signaling in axon guidance. J Biol Chem 288:1883–1895

    Article  CAS  PubMed  Google Scholar 

  • Rao Y (2005) Dissecting Nck/Dock signaling pathways in Drosophila visual system. Int J Biol Sci 1(2):80–86

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rapoport SI (1988) Brain evolution and Alzheimer’s disease. Rev Neurol 144:79–90

    CAS  PubMed  Google Scholar 

  • Reeves RH, Gearhart JD, Littlefield JW (1986) Genetic basis for a mouse model of Down syndrome. Brain Res Bull 16:803–814

    Article  CAS  PubMed  Google Scholar 

  • Rosso S, Bollati F, Bisbal M, Peretti D, Sumi T, Nakamura T, Quiroga S, Ferreira A, Cáceres A (2004) LIMK1 regulates Golgi dynamics, traffic of Golgi-derived vesicles, and process extension in primary cultured neurons. Mol Biol Cell 15(7):3433–3434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rousseau V, Goupille O, Morin N, Barnier JV (2003) A new constitutively active brain PAK3 isoform displays modified specificities toward Rac and Cdc42 GTPases. J Biol Chem 278(6):3912–3920

    Article  CAS  PubMed  Google Scholar 

  • Saito Y, Oka A, Mizuguchi M, Motonaga K, Mori Y, Becker LE, Arima K, Miyauchi J, Takashima S (2000) The developmental and aging changes of Down’s syndrome cell adhesion molecule expression in normal and Down’s syndrome brains. Acta Neuropathol (Berl) 100:654–664

    Article  CAS  Google Scholar 

  • Saud K, Arriagada C, Cárdenas AM, Shimahara T, Allen DD, Caviedes R, Caviedes P (2006) Neuronal dysfunction in Down syndrome: contribution of neuronal models in cell culture. J Physiol 99:201–210

    Google Scholar 

  • Schapiro MB, Creasey H, Schwartz M, Haxby JV, White B, Moore A, Rapoport SI (1987) Quantitative CT analysis of brain morphometry in adult Down’s syndrome at different ages. Neurology 37:1424–1427

    Article  CAS  PubMed  Google Scholar 

  • Schapiro MB, Luxenberg JS, Kaye JA, Haxby JV, Friedland R, Rapoport SI (1989) Serial quantitative CT analysis of brain morphometrics in adult Down’s syndrome at different ages. Neurology 39:1349–1353

    Article  CAS  PubMed  Google Scholar 

  • Schmidt-Sidor B, Wisniewski KE, Shepard TH, Sersen EA (1990) Brain growth in Down syndrome subjects 15 to 22 weeks of gestational age and birth to 60 months. Clin Neuropathol 9:181–190

    CAS  PubMed  Google Scholar 

  • Schmucker D, Chen B (2009) Dscam and DSCAM: complex genes in simple animals, complex animals yet simple genes. Genes Dev 23(2):147–156

    Article  CAS  PubMed  Google Scholar 

  • Takashima S, Becker LE, Armstrong DL, Chan F (1981) Abnormal neuronal development in the visual cortex of the human fetus and infant with Down’s syndrome. A quantitative and qualitative Golgi study. Brain Res 225:1–21

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Fu M, Wang L, Liu J, Li Y, Brakebusch C, Mei Q (2013) p21-activated kinase 1 (PAK1) can promote ERK activation in a kinase-independent manner. J Biol Chem 288(27):20093–20099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilson L, Curtis A, Korenberg JR, Schipper RD, Allan L, Chenevix-Trench G, Stephenson A, Goodship J, Burn J (1993) A large, dominant pedigree of atrioventricular septal defect (AVSD): exclusion from the Down syndrome critical region on chromosome 21. Am J Hum Genet 53(6):1262–1268

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wisniewski KE, Wisniewski HM, Wen GY (1985) Occurrence of neuropathological changes and dementia of Alzheimer’s disease in Down’s syndrome. Ann Neurol 17:278–282

    Article  CAS  PubMed  Google Scholar 

  • Wu Ch, Fallini C, Ticozzi N, Keagle P, Sapp P, Piotrowska K, Lowe P, Koppers M, McKenna-Yasek D, Baron D, Kost J, Gonzalez-Perez P, Fox A, Adams J, Taroni F, Tiloca C, Leclerc A, Chafe S, Mangroo D, Moore M, Zitzewitz J, Xu Z, van den Berg L, Glass J, Siciliano G, Cirulli E, Goldstein D, Salachas F, Meininger V, Rossoll W, Ratti A, Gellera C, Bosco D, Bassell G, Silani V, Drory V, Brown R, Landers J (2012) Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature 488:499–503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yates CM, Simpson J, Gordon A, Maloney AFJ, Allison Y, Ritchie IM, Urquart A (1983) Catecholamines and cholinergic enzymes in pre-senile and senile Alzheimer-type dementia and Down’s syndrome. Brain Res 280:119–126

    Article  CAS  PubMed  Google Scholar 

  • Yu J, Chung K, Deo M, Thompson R, Turner D (2008) MicroRNA miR-124 regulates neurite outgrowth during neuronal differentiation. Exp Cell Res 314:2618–2633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was funded by Fondecyt Grant #1130241 (Chile) to PC, and by The Fondation pour la Recherche sur le Cerveau (FRC) and the Fondation Jérôme Lejeune (J-V. B., France). PC holds patent protection for the CNh and CTb cell lines.

Author information

Authors and Affiliations

  1. Program of Molecular & Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Independencia, 1027, Santiago, Chile

    Ramón Pérez-Núñez, Natalia Barraza & Pablo Caviedes MD, PhD

  2. CINV, University of Valparaíso, Valparaíso, Chile

    Arlek Gonzalez-Jamett & Ana Maria Cárdenas

  3. Neuroscience Paris-Saclay Institute, UMR 9197, CNRS-Université Paris-Sud, 91400, Orsay Cedex, France

    Jean-Vianney Barnier

Authors
  1. Ramón Pérez-Núñez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Natalia Barraza
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Arlek Gonzalez-Jamett
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ana Maria Cárdenas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jean-Vianney Barnier
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pablo Caviedes MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pablo Caviedes MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pérez-Núñez, R., Barraza, N., Gonzalez-Jamett, A. et al. Overexpressed Down Syndrome Cell Adhesion Molecule (DSCAM) Deregulates P21-Activated Kinase (PAK) Activity in an In Vitro Neuronal Model of Down Syndrome: Consequences on Cell Process Formation and Extension. Neurotox Res 30, 76–87 (2016). https://doi.org/10.1007/s12640-016-9613-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12640-016-9613-9

Keywords

Search

Navigation