title: Effects of Mecp2 loss of function in embryonic cortical neurons: a bioinformatics strategy to sort out non-neuronal cells variability from transcriptome profiling.
abstract: BACKGROUND
  Mecp2 null mice model Rett syndrome (RTT) a human neurological disorder affecting females after apparent normal pre- and peri-natal developmental periods. Neuroanatomical studies in cerebral cortex of RTT mouse models revealed delayed maturation of neuronal morphology and autonomous as well as non-cell autonomous reduction in dendritic complexity of postnatal cortical neurons. However, both morphometric parameters and high-resolution expression profile of cortical neurons at embryonic developmental stage have not yet been studied. Here we address these topics by using embryonic neuronal primary cultures from Mecp2 loss of function mouse model.
  
  
  RESULTS
  We show that embryonic primary cortical neurons of Mecp2 null mice display reduced neurite complexity possibly reflecting transcriptional changes. We used RNA-sequencing coupled with a bioinformatics comparative approach to identify and remove the contribution of variable and hard to quantify non-neuronal brain cells present in our in vitro cell cultures.
  
  
  CONCLUSIONS
  Our results support the need to investigate both Mecp2 morphological as well as molecular effect in neurons since prenatal developmental stage, long time before onset of Rett symptoms.
authors.affiliation: Institute of Genetics and Biophysics "A. Buzzati Traverso", National Research Council (CNR)-80131, Naples, Italy. marcella.vacca@igb.cnr.it.
authors.forename: Marcella
authors.initials: M
authors.lastname: Vacca
authors.affiliation: Laboratory for Genomics, Transcriptomics and Proteomics (LAB-GTP), High Performance Computing and Networking Institute (ICAR), National Research Council (CNR)-80131, Naples, Italy. kumpar@na.icar.cnr.it.
authors.forename: Kumar Parijat
authors.initials: KP
authors.lastname: Tripathi
authors.affiliation: Institute of Genetics and Biophysics "A. Buzzati Traverso", National Research Council (CNR)-80131, Naples, Italy. speranza@igb.cnr.it.
authors.forename: Luisa
authors.initials: L
authors.lastname: Speranza
authors.affiliation: Sequentia Biotech SL, Calle Comte D'Urgell, 240 08036, Barcelona, Spain. raiesecigliano@sequentiabiotech.com.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Aiese Cigliano
authors.affiliation: IRCCS Neuromed, via dell'Elettronica, Pozzilli (Is), Italy. francesco.scalabri@neuromed.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Scalabrì
authors.affiliation: IRCCS Neuromed, via dell'Elettronica, Pozzilli (Is), Italy. federico.marracino@neuromed.it.
authors.forename: Federico
authors.initials: F
authors.lastname: Marracino
authors.affiliation: IRCCS Neuromed, via dell'Elettronica, Pozzilli (Is), Italy. stabulario@neuromed.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Madonna
authors.affiliation: Sequentia Biotech SL, Calle Comte D'Urgell, 240 08036, Barcelona, Spain. wsanseverino@sequentiabiotech.com.
authors.forename: Walter
authors.initials: W
authors.lastname: Sanseverino
authors.affiliation: Institute of Genetics and Biophysics "A. Buzzati Traverso", National Research Council (CNR)-80131, Naples, Italy. carla.perrone@igb.cnr.it.|Department of Pharmacy, University of Naples Federico II, Naples, Italy. carla.perrone@igb.cnr.it.
authors.forename: Carla
authors.initials: C
authors.lastname: Perrone-Capano
authors.affiliation: Laboratory for Genomics, Transcriptomics and Proteomics (LAB-GTP), High Performance Computing and Networking Institute (ICAR), National Research Council (CNR)-80131, Naples, Italy. mario.guarracino@cnr.it.
authors.forename: Mario Rosario
authors.initials: MR
authors.lastname: Guarracino
authors.affiliation: Institute of Genetics and Biophysics "A. Buzzati Traverso", National Research Council (CNR)-80131, Naples, Italy. maurizio.desposito@igb.cnr.it.|IRCCS Neuromed, via dell'Elettronica, Pozzilli (Is), Italy. maurizio.desposito@igb.cnr.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: D'Esposito
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000196:embryology / Q000378:metabolism / Q000473:pathology*; D002540:Cerebral Cortex / Q000378:metabolism; D019295:Computational Biology; D003712:Dendrites / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D051379:Mice; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000166:cytology; D015518:Rett Syndrome / Q000196:embryology* / Q000235:genetics* / Q000473:pathology; D017423:Sequence Analysis, RNA
chemical_list: C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2
references.citation: J Neurosci. 2014 Sep 17;34(38):12877-83
references.pmid: 25232122
references.citation: Bioinformatics. 2015 Jan 15;31(2):166-9
references.pmid: 25260700
references.citation: Dis Model Mech. 2012 Nov;5(6):733-45
references.pmid: 23115203
references.citation: J Neurochem. 1991 Feb;56(2):392-9
references.pmid: 1671084
references.citation: Science. 2000 Oct 27;290(5492):739-44
references.pmid: 11052929
references.citation: PLoS One. 2008;3(11):e3669
references.pmid: 18989361
references.citation: Ann Neurol. 2009 Dec;66(6):843-57
references.pmid: 20035504
references.citation: Nat Genet. 2001 Mar;27(3):322-6
references.pmid: 11242117
references.citation: BMC Bioinformatics. 2014 Aug 29;15:293
references.pmid: 25176396
references.citation: PLoS One. 2015 Nov 18;10(11):e0140268
references.pmid: 26581084
references.citation: Bioinformatics. 2010 Jan 1;26(1):139-40
references.pmid: 19910308
references.citation: Nucleic Acids Res. 2004 Mar 19;32(5):1818-23
references.pmid: 15034150
references.citation: Neurobiol Dis. 2001 Oct;8(5):847-65
references.pmid: 11592853
references.citation: J Neurosci. 2010 Apr 14;30(15):5346-56
references.pmid: 20392956
references.citation: Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8862-7
references.pmid: 11438693
references.citation: J Neurosci. 2008 Aug 13;28(33):8246-56
references.pmid: 18701687
references.citation: PLoS One. 2012;7(10):e47848
references.pmid: 23112857
references.citation: J Neurosci. 2013 Nov 27;33(48):18764-74
references.pmid: 24285883
references.citation: RNA Biol. 2013 Nov;10(11):1741-57
references.pmid: 24270455
references.citation: Bioinformatics. 2009 May 1;25(9):1105-11
references.pmid: 19289445
references.citation: Nat Neurosci. 2009 Mar;12(3):311-7
references.pmid: 19234456
references.citation: Mol Autism. 2013 Jan 25;4(1):3
references.pmid: 23351786
references.citation: Science. 2008 May 30;320(5880):1224-9
references.pmid: 18511691
references.citation: Hum Mol Genet. 2006 Jun 15;15(12):2003-14
references.pmid: 16682435
references.citation: Front Genet. 2012 Sep 11;3:181
references.pmid: 22973303
references.citation: BMC Med Genet. 2007 Jun 20;8:36
references.pmid: 17584923
references.citation: Nat Genet. 2001 Mar;27(3):327-31
references.pmid: 11242118
references.citation: Nucleic Acids Res. 2009 Jan;37(1):1-13
references.pmid: 19033363
references.citation: J Neurobiol. 2003 Apr;55(1):86-96
references.pmid: 12605461
references.citation: Cell Rep. 2014 Sep 11;8(5):1271-9
references.pmid: 25159150
references.citation: Nat Neurosci. 2000 Nov;3 Suppl:1171-7
references.pmid: 11127834
references.citation: Bioinformatics. 2014 Aug 1;30(15):2114-20
references.pmid: 24695404
references.citation: Bioinformatics. 2013 Sep 1;29(17):2146-52
references.pmid: 23821648
references.citation: Neurobiol Dis. 2013 Nov;59:257-66
references.pmid: 23948639
references.citation: Nat Genet. 2004 Apr;36(4):339-41
references.pmid: 15034579
references.citation: Cereb Cortex. 2000 Oct;10(10):981-91
references.pmid: 11007549
references.citation: PLoS One. 2014 Mar 25;9(3):e92169
references.pmid: 24667344
references.citation: Hum Mol Genet. 2007 Mar 15;16(6):640-50
references.pmid: 17309881
references.citation: Front Cell Neurosci. 2014 Feb 05;8:18
references.pmid: 24550777
references.citation: Nat Neurosci. 2013 Dec;16(12):1896-905
references.pmid: 24162652
references.citation: J Neurosci. 2009 Apr 22;29(16):5051-61
references.pmid: 19386901
references.citation: Nature. 2015 Jun 4;522(7554):89-93
references.pmid: 25762136
references.citation: J Neurosci. 2015 Mar 11;35(10):4386-402
references.pmid: 25762682
references.citation: Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10444-9
references.pmid: 16801538
references.citation: Nat Neurosci. 2004 Feb;7(2):145-52
references.pmid: 14730308
references.citation: Wien Med Wochenschr. 1966 Sep 10;116(37):723-6
references.pmid: 5300597
references.citation: Nat Genet. 1999 Oct;23(2):185-8
references.pmid: 10508514
references.citation: Glia. 2002 Dec;40(3):350-9
references.pmid: 12420314
references.citation: Biotechniques. 2003 Feb;34(2):374-8
references.pmid: 12613259
references.citation: Nat Neurosci. 2013 Apr;16(4):499-506
references.pmid: 23416452
references.citation: J Neurosci. 2008 Jan 2;28(1):264-78
references.pmid: 18171944
references.citation: J Neurochem. 2014 Oct;131(1):115-27
references.pmid: 24978323
references.citation: Ann Neurol. 2010 Dec;68(6):944-50
references.pmid: 21154482
references.citation: Cytometry A. 2010 Dec;77(12):1160-8
references.pmid: 20687200
references.citation: Nat Neurosci. 2006 Jan;9(1):99-107
references.pmid: 16369481
references.citation: Mol Biol Cell. 2005 Nov;16(11):5103-14
references.pmid: 16120643
references.citation: Mol Cell Neurosci. 2004 Nov;27(3):306-21
references.pmid: 15519245
references.citation: Science. 2007 Feb 23;315(5815):1143-7
references.pmid: 17289941
references.citation: Hum Mol Genet. 2009 Jul 1;18(13):2431-42
references.pmid: 19369296
references.citation: Nature. 1980 Nov 27;288(5789):370-3
references.pmid: 7432535
references.citation: Neurobiol Dis. 2011 Jul;43(1):190-200
references.pmid: 21420494
references.citation: PLoS One. 2009;4(3):e4977
references.pmid: 19305503
references.citation: J Comp Neurol. 2008 May 1;508(1):184-95
references.pmid: 18306326
references.citation: Brain Res. 2014 Jan 16;1543:151-8
references.pmid: 24269336
references.citation: Cell Stem Cell. 2013 Oct 3;13(4):446-58
references.pmid: 24094325
references.citation: Nat Protoc. 2009;4(1):44-57
references.pmid: 19131956
references.citation: PLoS One. 2011 Jan 27;6(1):e16493
references.pmid: 21304595
references.citation: J Neurosci. 2009 Sep 9;29(36):11172-81
references.pmid: 19741124
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 8;105(27):9391-6
references.pmid: 18599438
references.citation: J Neuropathol Exp Neurol. 2005 Jun;64(6):537-44
references.pmid: 15977646
references.citation: Cell. 2008 Nov 14;135(4):738-48
references.pmid: 19013281
references.citation: BMC Bioinformatics. 2013 Jul 09;14:219
references.pmid: 23837715
references.citation: Hum Mol Genet. 2002 Jan 15;11(2):115-24
references.pmid: 11809720