Skip to main content
SpringerLink
Log in

Lamin A/C Is Required for ChAT-Dependent Neuroblastoma Differentiation

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

The mouse neuroblastoma N18TG2 clone is unable to differentiate and is defective for the enzymes of the biosynthesis of neurotransmitters. The forced expression of choline acetyltransferase (ChAT) in these cells results in the synthesis and release of acetylcholine (Ach) and hence in the expression of neurospecific features and markers. To understand how the expression of ChAT triggered neuronal differentiation, we studied the differences in genome-wide transcription profiles between the N18TG2 parental cells and its ChAT-expressing 2/4 derived clone. The engagement of the 2/4 cells in the neuronal developmental program was confirmed by the increase of the expression level of several differentiation-related genes and by the reduction of the amount of transcripts of cell cycle genes. At the same time, we observed a massive reorganization of cytoskeletal proteins in terms of gene expression, with the accumulation of the nucleoskeletal lamina component Lamin A/C in differentiating cells. The increase of the Lmna transcripts induced by ChAT expression in 2/4 cells was mimicked treating the parental N18TG2 cells with the acetylcholine receptor agonist carbachol, thus demonstrating the direct role played by this receptor in neuron nuclei maturation. Conversely, a treatment of 2/4 cells with the muscarinic receptor antagonist atropine resulted in the reduction of the amount of Lmna RNA. Finally, the hypothesis that Lmna gene product might play a crucial role in the ChAT-dependent molecular differentiation cascade was strongly supported by Lmna knockdown in 2/4 cells leading to the downregulation of genes involved in differentiation and cytoskeleton formation and to the upregulation of genes known to regulate self-renewal and stemness.

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
Fig. 7

Similar content being viewed by others

References

  1. Nguyen L, Rigo JM, Rocher V, Belachew S, Malgrange B, Rogister B, Leprince P, Moonen G (2001) Neurotransmitters as early signals for central nervous system development. Cell Tissue Res 305(2):187–202

    Article  CAS  PubMed  Google Scholar 

  2. Lauder JM (1993) Neurotransmitters as growth regulatory signals: role of receptors and second messengers. Trends Neurosci 16(6):233–240

    Article  CAS  PubMed  Google Scholar 

  3. Mattson MP, Furukawa K (1998) Signaling events regulating the neurodevelopmental triad. Glutamate and secreted forms of beta-amyloid precursor protein as examples. Perspect Dev Neurobiol 5(4):337–352

    CAS  PubMed  Google Scholar 

  4. Bovetti S, Gribaudo S, Puche AC, De Marchis S, Fasolo A (2011) From progenitors to integrated neurons: role of neurotransmitters in adult olfactory neurogenesis. J Chem Neuroanat 42(4):304–316. doi:10.1016/j.jchemneu.2011.05.006

    Article  CAS  PubMed  Google Scholar 

  5. Horiuchi Y, Kimura R, Kato N, Fujii T, Seki M, Endo T, Kato T, Kawashima K (2003) Evolutional study on acetylcholine expression. Life Sci 72(15):1745–1756

    Article  CAS  PubMed  Google Scholar 

  6. Wessler I, Kirkpatrick CJ (2008) Acetylcholine beyond neurons: the non-neuronal cholinergic system in humans. Br J Pharmacol 154(8):1558–1571. doi:10.1038/bjp.2008.185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ruediger T, Bolz J (2007) Neurotransmitters and the development of neuronal circuits. In: Bagnard D (ed) Axon growth and guidance. Landes Bioscience and Springer Science

  8. Nelson P, Christian C, Niremberg M (1976) Synapse formation between clonal neuroblastoma x glioma hybrid cells and striated muscle cells. Proc Natl Acad Sci U S A 73:123–127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hamprecht B (1977) Structural, electrophysiological, biochemical, and pharmacological properties of neuroblastoma-glioma cell hybrids in cell culture. Int Rev Cytol 49:99–170

    Article  CAS  PubMed  Google Scholar 

  10. Bignami F, Bevilacqua P, Biagioni S, De Jaco A, Casamenti F, Felsani A, Augusti-Tocco G (1997) Cellular acetylcholine content and neuronal differentiation. J Neurochem 69(4):1374–1381

    Article  CAS  PubMed  Google Scholar 

  11. Biagioni S, Tata AM, De Jaco A, Augusti-Tocco G (2000) Acetylcholine synthesis and neuron differentiation. Int J Dev Biol 44(6):689–697

    CAS  PubMed  Google Scholar 

  12. De Jaco A, Augusti-Tocco G, Biagioni S (2002) Muscarinic acetylcholine receptors induce neurite outgrowth and activate the synapsin I gene promoter in neuroblastoma clones. Neuroscience 113(2):331–338

    Article  PubMed  Google Scholar 

  13. Salani M, Anelli T, Tocco GA, Lucarini E, Mozzetta C, Poiana G, Tata AM, Biagioni S (2009) Acetylcholine-induced neuronal differentiation: muscarinic receptor activation regulates EGR-1 and REST expression in neuroblastoma cells. J Neurochem 108(3):821–834. doi:10.1111/j.1471-4159.2008.05829.x

    Article  CAS  PubMed  Google Scholar 

  14. Kapitein LC, Hoogenraad CC (2015) Building the neuronal microtubule cytoskeleton. Neuron 87(3):492–506. doi:10.1016/j.neuron.2015.05.046

    Article  CAS  PubMed  Google Scholar 

  15. Volk T (2013) Positioning nuclei within the cytoplasm of striated muscle fiber: cooperation between microtubules and KASH proteins. Nucleus 4(1):18–22. doi:10.4161/nucl.23086

    Article  PubMed  PubMed Central  Google Scholar 

  16. Elhanany-Tamir H, Yu YV, Shnayder M, Jain A, Welte M, Volk T (2012) Organelle positioning in muscles requires cooperation between two KASH proteins and microtubules. J Cell Biol 198(5):833–846. doi:10.1083/jcb.201204102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Razafsky DS, Ward CL, Kolb T, Hodzic D (2013) Developmental regulation of linkers of the nucleoskeleton to the cytoskeleton during mouse postnatal retinogenesis. Nucleus 4(5):399–409. doi:10.4161/nucl.26244

    Article  PubMed  PubMed Central  Google Scholar 

  18. Razafsky D, Blecher N, Markov A, Stewart-Hutchinson PJ, Hodzic D (2012) LINC complexes mediate the positioning of cone photoreceptor nuclei in mouse retina. PLoS One 7(10):e47180. doi:10.1371/journal.pone.0047180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Aebi U, Cohn J, Buhle L, Gerace L (1986) The nuclear lamina is a meshwork of intermediate-type filaments. Nature 323(6088):560–564. doi:10.1038/323560a0

    Article  CAS  PubMed  Google Scholar 

  20. Sullivan T, Escalante-Alcalde D, Bhatt H, Anver M, Bhat N, Nagashima K, Stewart CL, Burke B (1999) Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. J Cell Biol 147(5):913–920

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Constantinescu D, Gray HL, Sammak PJ, Schatten GP, Csoka AB (2006) Lamin A/C expression is a marker of mouse and human embryonic stem cell differentiation. Stem Cells 24(1):177–185. doi:10.1634/stemcells.2004-0159

    Article  CAS  PubMed  Google Scholar 

  22. Maresca G, Natoli M, Nardella M, Arisi I, Trisciuoglio D, Desideri M, Brandi R, D’Aguanno S et al (2012) LMNA knock-down affects differentiation and progression of human neuroblastoma cells. PLoS One 7(9):e45513. doi:10.1371/journal.pone.0045513

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Nardella M, Guglielmi L, Musa C, Iannetti I, Maresca G, Amendola D, Porru M, Carico E, Sessa G, Camerlingo R, Dominici C, Megiorni F, Milan M, Bearzi C, Rizzi R, Pirozzi G, Leonetti C, Bucci B, Mercanti D, Felsani A, D’Agnano I (2015) Down-regulation of the Lamin A/C in neuroblastoma triggers the expansion of tumor initiating cells. 2015

  24. Vanburen V, Chen H (2012) Managing biological complexity across orthologs with a visual knowledgebase of documented biomolecular interactions. Sci Rep 2:1011. doi:10.1038/srep01011

    Article  PubMed  PubMed Central  Google Scholar 

  25. Herlenius E, Lagercrantz H (2001) Neurotransmitters and neuromodulators during early human development. Early Hum Dev 65(1):21–37. doi:10.1016/S0378-3782(01)00189-X

    Article  CAS  PubMed  Google Scholar 

  26. Bolz TRaJ (2007) Neurotransmitters and the development of neuronal circuits. In: Bagnard D (ed) Axon growth and guidance. Landes Bioscience and Springer Science+ Business Media pp 104–115

  27. Berg DA, Belnoue L, Song H, Simon A (2013) Neurotransmitter-mediated control of neurogenesis in the adult vertebrate brain. Development 140(12):2548–2561. doi:10.1242/dev.088005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Pathania M, Yan LD, Bordey A (2010) A symphony of signals conducts early and late stages of adult neurogenesis. Neuropharmacology 58(6):865–876. doi:10.1016/j.neuropharm.2010.01.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Benninghoff J, Rauh W, Brantl V, Schloesser RJ, Moessner R, Moller HJ, Rujescu D (2013) Cholinergic impact on neuroplasticity drives muscarinic M1 receptor mediated differentiation into neurons. World J Biol Psychiatry 14(3):241–246. doi:10.3109/15622975.2011.624121

    Article  PubMed  Google Scholar 

  30. Ma W, Maric D, Li BS, Hu Q, Andreadis JD, Grant GM, Liu QY, Shaffer KM et al (2000) Acetylcholine stimulates cortical precursor cell proliferation in vitro via muscarinic receptor activation and MAP kinase phosphorylation. Eur J Neurosci 12(4):1227–1240

    Article  CAS  PubMed  Google Scholar 

  31. Politis PK, Makri G, Thomaidou D, Geissen M, Rohrer H, Matsas R (2007) BM88/CEND1 coordinates cell cycle exit and differentiation of neuronal precursors. Proc Natl Acad Sci U S A 104(45):17861–17866. doi:10.1073/pnas.0610973104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Huang C, Qin D (2010) Role of Lef1 in sustaining self-renewal in mouse embryonic stem cells. J Genet Genomics 37(7):441–449. doi:10.1016/S1673-8527(09)60063-1

    Article  CAS  PubMed  Google Scholar 

  33. Lendahl U, Zimmerman LB, McKay RD (1990) CNS stem cells express a new class of intermediate filament protein. Cell 60(4):585–595

    Article  CAS  PubMed  Google Scholar 

  34. Hockfield S, McKay RD (1985) Identification of major cell classes in the developing mammalian nervous system. J Neurosci Off J Soc Neurosci 5(12):3310–3328

    CAS  Google Scholar 

  35. Weigmann A, Corbeil D, Hellwig A, Huttner WB (1997) Prominin, a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells, is targeted to plasmalemmal protrusions of non-epithelial cells. Proc Natl Acad Sci U S A 94(23):12425–12430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Corbeil D, Karbanova J, Fargeas CA, Jaszai J (2013) Prominin-1 (CD133): molecular and cellular features across species. Adv Exp Med Biol 777:3–24. doi:10.1007/978-1-4614-5894-4_1

    Article  PubMed  Google Scholar 

  37. Hall DH, Treinin M (2011) How does morphology relate to function in sensory arbors? Trends Neurosci 34(9):443–451. doi:10.1016/j.tins.2011.07.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Sasaki T, Matsuki N, Ikegaya Y (2012) Effects of axonal topology on the somatic modulation of synaptic outputs. J Neurosci Off J Soc Neurosci 32(8):2868–2876. doi:10.1523/JNEUROSCI.5365-11.2012

    Article  CAS  Google Scholar 

  39. Stewart E, Shen K (2015) STORMing towards a clear picture of the cytoskeleton in neurons. eLife 4. doi:10.7554/eLife.06235

  40. Bennett V, Lorenzo DN (2013) Spectrin- and ankyrin-based membrane domains and the evolution of vertebrates. Curr Top Membr 72:1–37. doi:10.1016/B978-0-12-417027-8.00001-5

    Article  CAS  PubMed  Google Scholar 

  41. Kapitein LC, Hoogenraad CC (2011) Which way to go? Cytoskeletal organization and polarized transport in neurons. Mol Cell Neurosci 46(1):9–20. doi:10.1016/j.mcn.2010.08.015

    Article  CAS  PubMed  Google Scholar 

  42. Machnicka B, Czogalla A, Hryniewicz-Jankowska A, Boguslawska DM, Grochowalska R, Heger E, Sikorski AF (2014) Spectrins: a structural platform for stabilization and activation of membrane channels, receptors and transporters. Biochim Biophys Acta 1838(2):620–634. doi:10.1016/j.bbamem.2013.05.002

    Article  CAS  PubMed  Google Scholar 

  43. Susuki K, Rasband MN (2008) Spectrin and ankyrin-based cytoskeletons at polarized domains in myelinated axons. Exp Biol Med (Maywood) 233(4):394–400. doi:10.3181/0709-MR-243

    Article  CAS  Google Scholar 

  44. Causeret F, Jacobs T, Terao M, Heath O, Hoshino M, Nikolic M (2007) Neurabin-I is phosphorylated by Cdk5: implications for neuronal morphogenesis and cortical migration. Mol Biol Cell 18(11):4327–4342. doi:10.1091/mbc.E07-04-0372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kawauchi T (2014) Cdk5 regulates multiple cellular events in neural development, function and disease. Dev Growth Differ 56(5):335–348. doi:10.1111/dgd.12138

    Article  CAS  PubMed  Google Scholar 

  46. Tanabe K, Yamazaki H, Inaguma Y, Asada A, Kimura T, Takahashi J, Taoka M, Ohshima T et al (2014) Phosphorylation of drebrin by cyclin-dependent kinase 5 and its role in neuronal migration. PLoS One 9(3):e92291. doi:10.1371/journal.pone.0092291

    Article  PubMed  PubMed Central  Google Scholar 

  47. Shah K, Lahiri DK (2014) Cdk5 activity in the brain—multiple paths of regulation. J Cell Sci 127(Pt 11):2391–2400. doi:10.1242/jcs.147553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Tischfield MA, Baris HN, Wu C, Rudolph G, Van Maldergem L, He W, Chan WM, Andrews C et al (2010) Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance. Cell 140(1):74–87. doi:10.1016/j.cell.2009.12.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Qu C, Dwyer T, Shao Q, Yang T, Huang H, Liu G (2013) Direct binding of TUBB3 with DCC couples netrin-1 signaling to intracellular microtubule dynamics in axon outgrowth and guidance. J Cell Sci 126(Pt 14):3070–3081. doi:10.1242/jcs.122184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. van Haren J, Draegestein K, Keijzer N, Abrahams JP, Grosveld F, Peeters PJ, Moechars D, Galjart N (2009) Mammalian navigators are microtubule plus-end tracking proteins that can reorganize the cytoskeleton to induce neurite-like extensions. Cell Motil Cytoskeleton 66(10):824–838. doi:10.1002/cm.20370

    Article  PubMed  Google Scholar 

  51. Wanschers B, van de Vorstenbosch R, Wijers M, Wieringa B, King SM, Fransen J (2008) Rab6 family proteins interact with the dynein light chain protein DYNLRB1. Cell Motil Cytoskeleton 65(3):183–196. doi:10.1002/cm.20254

    Article  CAS  PubMed  Google Scholar 

  52. Street M, Marsh SJ, Stabach PR, Morrow JS, Brown DA, Buckley NJ (2006) Stimulation of Galphaq-coupled M1 muscarinic receptor causes reversible spectrin redistribution mediated by PLC, PKC and ROCK. J Cell Sci 119(Pt 8):1528–1536. doi:10.1242/jcs.02872

    Article  CAS  PubMed  Google Scholar 

  53. Teber I, Kohling R, Speckmann EJ, Barnekow A, Kremerskothen J (2004) Muscarinic acetylcholine receptor stimulation induces expression of the activity-regulated cytoskeleton-associated gene (ARC). Brain Res Mol Brain Res 121(1–2):131–136. doi:10.1016/j.molbrainres.2003.11.017

    Article  CAS  PubMed  Google Scholar 

  54. Belyantseva IA, Perrin BJ, Sonnemann KJ, Zhu M, Stepanyan R, McGee J, Frolenkov GI, Walsh EJ et al (2009) Gamma-actin is required for cytoskeletal maintenance but not development. Proc Natl Acad Sci U S A 106(24):9703–9708. doi:10.1073/pnas.0900221106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Navratil AM, Dozier MG, Whitesell JD, Clay CM, Roberson MS (2014) Role of cortactin in dynamic actin remodeling events in gonadotrope cells. Endocrinology 155(2):548–557. doi:10.1210/en.2012-1924

    Article  PubMed  Google Scholar 

  56. Yokoyama T, Copeland NG, Jenkins NA, Montgomery CA, Elder FF, Overbeek PA (1993) Reversal of left-right asymmetry: a situs inversus mutation. Science 260(5108):679–682

    Article  CAS  PubMed  Google Scholar 

  57. Arstikaitis P, Gauthier-Campbell C, Carolina Gutierrez Herrera R, Huang K, Levinson JN, Murphy TH, Kilimann MW, Sala C et al (2008) Paralemmin-1, a modulator of filopodia induction is required for spine maturation. Mol Biol Cell 19(5):2026–2038. doi:10.1091/mbc.E07-08-0802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Kang HJ, Voleti B, Hajszan T, Rajkowska G, Stockmeier CA, Licznerski P, Lepack A, Majik MS et al (2012) Decreased expression of synapse-related genes and loss of synapses in major depressive disorder. Nat Med 18(9):1413–1417. doi:10.1038/nm.2886

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Grigoriev I, Splinter D, Keijzer N, Wulf PS, Demmers J, Ohtsuka T, Modesti M, Maly IV et al (2007) Rab6 regulates transport and targeting of exocytotic carriers. Dev Cell 13(2):305–314. doi:10.1016/j.devcel.2007.06.010

    Article  CAS  PubMed  Google Scholar 

  60. Wiche G, Winter L (2011) Plectin isoforms as organizers of intermediate filament cytoarchitecture. Bioarchitecture 1(1):14–20. doi:10.4161/bioa.1.1.14630

    Article  PubMed  PubMed Central  Google Scholar 

  61. Zhang Q, Ragnauth C, Greener MJ, Shanahan CM, Roberts RG (2002) The nesprins are giant actin-binding proteins, orthologous to Drosophila melanogaster muscle protein MSP-300. Genomics 80(5):473–481

    Article  CAS  PubMed  Google Scholar 

  62. Wilhelmsen K, Litjens SH, Kuikman I, Tshimbalanga N, Janssen H, van den Bout I, Raymond K, Sonnenberg A (2005) Nesprin-3, a novel outer nuclear membrane protein, associates with the cytoskeletal linker protein plectin. J Cell Biol 171(5):799–810. doi:10.1083/jcb.200506083

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Haque F, Mazzeo D, Patel JT, Smallwood DT, Ellis JA, Shanahan CM, Shackleton S (2010) Mammalian SUN protein interaction networks at the inner nuclear membrane and their role in laminopathy disease processes. J Biol Chem 285(5):3487–3498. doi:10.1074/jbc.M109.071910

    Article  CAS  PubMed  Google Scholar 

  64. Dahl KN, Kalinowski A (2011) Nucleoskeleton mechanics at a glance. J Cell Sci 124(Pt 5):675–678. doi:10.1242/jcs.069096

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Zhong Z, Chang SA, Kalinowski A, Wilson KL, Dahl KN (2010) Stabilization of the spectrin-like domains of nesprin-1alpha by the evolutionarily conserved “adaptive” domain. Cell Mol Bioeng 3(2):139–150. doi:10.1007/s12195-010-0121-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Smith ER, Zhang XY, Capo-Chichi CD, Chen X, Xu XX (2011) Increased expression of Syne1/nesprin-1 facilitates nuclear envelope structure changes in embryonic stem cell differentiation. Dev Dyn Off Publ Am Assoc Anatomists 240(10):2245–2255. doi:10.1002/dvdy.22717

    CAS  Google Scholar 

  67. Schlager MA, Kapitein LC, Grigoriev I, Burzynski GM, Wulf PS, Keijzer N, de Graaff E, Fukuda M et al (2010) Pericentrosomal targeting of Rab6 secretory vesicles by Bicaudal-D-related protein 1 (BICDR-1) regulates neuritogenesis. EMBO J 29(10):1637–1651. doi:10.1038/emboj.2010.51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Huang DW, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4(1):44–57. doi:10.1038/nprot.2008.211

    Article  CAS  Google Scholar 

  69. Saeed AI, Bhagabati NK, Braisted JC, Liang W, Sharov V, Howe EA, Li J, Thiagarajan M et al (2006) TM4 microarray software suite. Methods Enzymol 411:134–193. doi:10.1016/S0076-6879(06)11009-5

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was partially supported by a Joint Grant CNR-EBRI “Molecular and cellular mechanisms of brain plasticity” and by PNR-CNR Aging Program 2012–2014. Authors affiliated to EBRI were supported by European FP7 PAINCAGE grant n.603191, coordinated by Antonino Cattaneo. The authors thank Dr. Delio Mercanti for his continuous and invaluable research support at CNR.

Author information

Authors and Affiliations

  1. CNR, Institute of Cell Biology and Neurobiology (IBCN), Rome, Italy

    Loredana Guglielmi, Marta Nardella, Carla Musa, Ilaria Iannetti, Igea D’Agnano & Armando Felsani

  2. Genomics Facility, European Brain Research Institute (EBRI), Rome, Italy

    Ivan Arisi, Mara D’Onofrio & Andrea Storti

  3. Department of Laboratory Medicine and Department of Internal Medicine, PTV, University of Rome “Tor Vergata”, Rome, Italy

    Alessandra Valentini

  4. Department of Biology and Biotechnology “Charles Darwin”, Sapienza University, Rome, Italy

    Emanuele Cacci, Stefano Biagioni & Gabriella Augusti-Tocco

Authors
  1. Loredana Guglielmi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marta Nardella
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carla Musa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ilaria Iannetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ivan Arisi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mara D’Onofrio
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Andrea Storti
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alessandra Valentini
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Emanuele Cacci
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Stefano Biagioni
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Gabriella Augusti-Tocco
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Igea D’Agnano
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Armando Felsani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Igea D’Agnano or Armando Felsani.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Supplementary Fig. S1

a. Divergence of expression pattern in N18TG2 and 2/4 cells after RA treatment. Correlation plot between Log2 intensity fluorescence values of 2/4 and N18TG2 cells in RA-treated conditions. The values reported compare transcripts modulation during RA stimulus for each cell line. b. Correlation of expression pattern in 2/4 cells. Correlation plot between Log2 intensity fluorescence values of 2/4 cells in untreated (CTR) and RA-treated conditions. The values reported compare transcripts modulation after RA treatment in 2/4 cells. (PDF 1385 kb)

Supplementary Table S1

Total gene expression data after filtering-out the transcripts with replicate values showing a coefficient of variation larger than 2.0 and those with replicate-averaged fluorescence intensity values below the background. (XLSX 9980 kb)

Supplementary Table S2

Functional gene categories found by analyzing with the DAVID tool the differentially expressed genes between 2/4 and N18TG2 cell lines in basal culture conditions. Upregulated and downregulated GO categories, along with the gene list belonging to each category, are reported in different worksheets. (XLSX 170 kb)

Supplementary Table S3

Functional gene categories found by analyzing with the DAVID tool the common and differentially expressed genes between 2/4 and N18TG2 cell lines after RA treatment. Common and differentially upregulated and downregulated GO categories, along with the gene list belonging to each category, are reported in different worksheets. (XLSX 225 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guglielmi, L., Nardella, M., Musa, C. et al. Lamin A/C Is Required for ChAT-Dependent Neuroblastoma Differentiation. Mol Neurobiol 54, 3729–3744 (2017). https://doi.org/10.1007/s12035-016-9902-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-016-9902-6

Keywords

Search

Navigation