title: Simulating cortical development as a self constructing process: a novel multi-scale approach combining molecular and physical aspects.
abstract: Current models of embryological development focus on intracellular processes such as gene expression and protein networks, rather than on the complex relationship between subcellular processes and the collective cellular organization these processes support. We have explored this collective behavior in the context of neocortical development, by modeling the expansion of a small number of progenitor cells into a laminated cortex with layer and cell type specific projections. The developmental process is steered by a formal language analogous to genomic instructions, and takes place in a physically realistic three-dimensional environment. A common genome inserted into individual cells control their individual behaviors, and thereby gives rise to collective developmental sequences in a biologically plausible manner. The simulation begins with a single progenitor cell containing the artificial genome. This progenitor then gives rise through a lineage of offspring to distinct populations of neuronal precursors that migrate to form the cortical laminae. The precursors differentiate by extending dendrites and axons, which reproduce the experimentally determined branching patterns of a number of different neuronal cell types observed in the cat visual cortex. This result is the first comprehensive demonstration of the principles of self-construction whereby the cortical architecture develops. In addition, our model makes several testable predictions concerning cell migration and branching mechanisms.
authors: Institute of Neuroinformatics, University of Zürich/Swiss Federal Institute of Technology Zürich, Switzerland. fred@ini.phys.ethz.ch
authors: Frederic
authors: F
authors: Zubler
authors: Andreas
authors: A
authors: Hauri
authors: Sabina
authors: S
authors: Pfister
authors: Roman
authors: R
authors: Bauer
authors: John C
authors: JC
authors: Anderson
authors: Adrian M
authors: AM
authors: Whatley
authors: Rodney J
authors: RJ
authors: Douglas
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D002415:Cats; D002465:Cell Movement / Q000502:physiology; D048430:Cell Shape; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D003712:Dendrites / Q000502:physiology; D053263:Gene Regulatory Networks / Q000502:physiology; D008959:Models, Neurological; D055495:Neurogenesis / Q000502:physiology*; D014793:Visual Cortex / Q000166:cytology*
references: PLoS Comput Biol. 2008 May 30;4(5):e1000078
references: 18516226
references: Front Comput Neurosci. 2011 Dec 08;5:57
references: 22163218
references: J Neurosci Methods. 1995 Feb;56(2):133-44
references: 7752679
references: Development. 2002 Jul;129(13):3147-60
references: 12070090
references: Trends Neurosci. 2008 Feb;31(2):90-8
references: 18201774
references: J Comp Neurol. 2002 Dec 2;454(1):1-14
references: 12410614
references: Brain Res. 1993 Apr 23;609(1-2):284-92
references: 8508310
references: Nat Rev Neurosci. 2002 Jun;3(6):423-32
references: 12042877
references: Nature. 2008 Jun 5;453(7196):745-50
references: 18463632
references: Neuron. 2004 Jul 22;43(2):251-9
references: 15260960
references: PLoS Biol. 2005 Aug;3(8):e272
references: 16026180
references: Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20374-9
references: 19091945
references: Nat Rev Mol Cell Biol. 2009 May;10(5):332-43
references: 19373241
references: Science. 2002 Mar 1;295(5560):1662-4
references: 11872829
references: Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):7030-5
references: 9192686
references: Dev Biol. 2007 May 15;305(2):695-713
references: 17412320
references: J Comp Neurol. 1997 Aug 18;385(1):95-116
references: 9268119
references: J Neurophysiol. 2008 May;99(5):2320-8
references: 18305091
references: Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3879-83
references: 11274408
references: Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):4936-42
references: 15788537
references: PLoS Comput Biol. 2011 Feb 10;7(2):e1001071
references: 21347315
references: Exp Neurol. 1959 Nov;1:491-527
references: 14435979
references: Neuroinformatics. 2009 Sep;7(3):195-210
references: 19672726
references: BMC Syst Biol. 2011 Sep 30;5:154
references: 21962057
references: J Physiol. 1984 Aug;353:463-504
references: 6481629
references: EURASIP J Bioinform Syst Biol. 2011;2011:616382
references: 21436988
references: Artif Life. 2007 Fall;13(4):347-68
references: 17716016
references: Nat Rev Neurosci. 2007 Jun;8(6):427-37
references: 17514196
references: J Theor Biol. 2009 Oct 21;260(4):589-97
references: 19615382
references: Science. 1997 Oct 17;278(5337):474-6
references: 9334308
references: J Comp Neurol. 1972 May;145(1):61-83
references: 4624784
references: EMBO J. 2011 May 4;30(9):1690-704
references: 21441895
references: Cereb Cortex. 2006 Jul;16 Suppl 1:i152-61
references: 16766701
references: PLoS Comput Biol. 2006 Mar;2(3):e22
references: 16557292
references: Bull Math Biol. 1992 Sep;54(5):759-84
references: 1638259
references: Anat Rec. 1970 Feb;166(2):257-61
references: 5414696
references: Prog Retin Eye Res. 2008 May;27(3):260-83
references: 18374618
references: J Physiol. 2011 Mar 1;589(Pt 5):1017-30
references: 21224238
references: Nature. 2006 Jun 29;441(7097):1068-74
references: 16810241
references: J Comp Neurol. 2004 Nov 1;479(1):1-14
references: 15389616
references: Eur J Neurosci. 2006 Feb;23(4):901-9
references: 16519655
references: Phys Biol. 2006 Sep 08;3(3):172-82
references: 17021381
references: Cell. 2008 Feb 22;132(4):583-97
references: 18295577
references: J Neurosci. 2008 Jan 2;28(1):143-53
references: 18171932
references: PLoS One. 2012;7(3):e33623
references: 22457779
references: Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20063-6
references: 19104053
references: Nat Neurosci. 2004 Feb;7(2):136-44
references: 14703572
references: Neuron. 2011 Oct 20;72(2):269-84
references: 22017987
references: PLoS Comput Biol. 2008 Jun 06;4(5):e1000089
references: 18483611
references: PLoS Comput Biol. 2008 Sep 19;4(9):e1000163
references: 18802455
references: Cereb Cortex. 2013 Mar;23(3):604-14
references: 22368082
references: Cereb Cortex. 2001 Nov;11(11):1027-39
references: 11590112
references: Nature. 1995 Apr 20;374(6524):719-23
references: 7715726
references: Proc Natl Acad Sci U S A. 2011 May 10;108(19):8015-20
references: 21518872
references: Nature. 2000 Apr 6;404(6778):567-73
references: 10766232
references: PLoS Comput Biol. 2009 Dec;5(12):e1000600
references: 20011124
references: Exp Neurol. 1990 Jan;107(1):48-62
references: 2295319
references: Nat Rev Neurosci. 2011 Jun;12(6):311-26
references: 21587288
references: J Neurosci. 1998 Oct 1;18(19):7930-40
references: 9742160
references: Nat Rev Neurosci. 2008 Feb;9(2):110-22
references: 18209730
references: Nat Neurosci. 2002 Oct;5(10):939-45
references: 12244323
references: Brain Res. 1971 Oct 29;33(2):471-6
references: 5002632
references: J Neurobiol. 2004 Apr;59(1):82-94
references: 15007829
references: Cereb Cortex. 2002 May;12(5):453-65
references: 11950763
references: Front Comput Neurosci. 2009 Nov 20;3:25
references: 19949465
references: J Neurosci. 2004 Sep 29;24(39):8441-53
references: 15456817
references: Differentiation. 1976 Aug 3;6(2):117-23
references: 1010155
references: J Anat. 1953 Oct;87(4):387-406
references: 13117757
references: J Neurosci. 2007 Nov 7;27(45):12242-54
references: 17989290
references: Nat Rev Neurosci. 2007 Jun;8(6):438-50
references: 17514197
references: Trends Neurosci. 2004 Jul;27(7):392-9
references: 15219738