title: Robustness under functional constraint: the genetic network for temporal expression in Drosophila neurogenesis.
abstract: Precise temporal coordination of gene expression is crucial for many developmental processes. One central question in developmental biology is how such coordinated expression patterns are robustly controlled. During embryonic development of the Drosophila central nervous system, neural stem cells called neuroblasts express a group of genes in a definite order, which leads to the diversity of cell types. We produced all possible regulatory networks of these genes and examined their expression dynamics numerically. From the analysis, we identified requisite regulations and predicted an unknown factor to reproduce known expression profiles caused by loss-of-function or overexpression of the genes in vivo, as well as in the wild type. Following this, we evaluated the stability of the actual Drosophila network for sequential expression. This network shows the highest robustness against parameter variations and gene expression fluctuations among the possible networks that reproduce the expression profiles. We propose a regulatory module composed of three types of regulations that is responsible for precise sequential expression. This study suggests that the Drosophila network for sequential expression has evolved to generate the robust temporal expression for neuronal specification.
authors.affiliation: Department of Basic Science, University of Tokyo, Komaba, Tokyo, Japan. nakajima@complex.c.u-tokyo.ac.jp
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nakajima
authors.forename: Takako
authors.initials: T
authors.lastname: Isshiki
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Kaneko
authors.forename: Shuji
authors.initials: S
authors.lastname: Ishihara
mesh_terms: D000818:Animals; D019521:Body Patterning; D004330:Drosophila / Q000196:embryology* / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D008954:Models, Biological; D015233:Models, Statistical; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons; D012044:Regression Analysis; D013234:Stem Cells / Q000502:physiology; D049490:Systems Biology / Q000379:methods; D013997:Time Factors
references.citation: Dev Dyn. 2005 Mar;232(3):609-16
references.pmid: 15704126
references.citation: J Theor Biol. 2003 Oct 21;224(4):517-37
references.pmid: 12957124
references.citation: J Theor Biol. 2008 May 7;252(1):131-44
references.pmid: 18342890
references.citation: Dev Cell. 2005 Feb;8(2):203-13
references.pmid: 15691762
references.citation: Development. 2008 Sep;135(18):3071-9
references.pmid: 18701546
references.citation: Dev Cell. 2001 Oct;1(4):453-65
references.pmid: 11703937
references.citation: PLoS One. 2008 Jul 23;3(7):e2772
references.pmid: 18648662
references.citation: Cell. 2001 Aug 24;106(4):511-21
references.pmid: 11525736
references.citation: Mol Syst Biol. 2006;2:70
references.pmid: 17170765
references.citation: Genes Dev. 2006 Sep 15;20(18):2618-27
references.pmid: 16980589
references.citation: Nature. 2000 Jul 13;406(6792):188-92
references.pmid: 10910359
references.citation: Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4781-6
references.pmid: 15037758
references.citation: Science. 2005 Sep 23;309(5743):2010-3
references.pmid: 16179466
references.citation: Philos Trans R Soc Lond B Biol Sci. 2008 Jan 12;363(1489):39-56
references.pmid: 17309865
references.citation: Genes Dev. 1998 Jan 15;12(2):246-60
references.pmid: 9436984
references.citation: PLoS Biol. 2004 Sep;2(9):E271
references.pmid: 15340490
references.citation: Genetics. 2004 Aug;167(4):1721-37
references.pmid: 15342511
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 16;102(33):11775-80
references.pmid: 16087882
references.citation: Nature. 1997 Jun 26;387(6636):913-7
references.pmid: 9202124
references.citation: Curr Biol. 2008 Jul 8;18(13):943-50
references.pmid: 18571409
references.citation: PLoS Biol. 2007 Feb;5(2):e37
references.pmid: 17298176
references.citation: PLoS Comput Biol. 2009 Mar;5(3):e1000303
references.pmid: 19282965
references.citation: Development. 1987 Sep;101(1):1-22
references.pmid: 2896587
references.citation: Dev Dyn. 2006 Apr;235(4):861-9
references.pmid: 16222713
references.citation: Genes Cells. 2005 Nov;10(11):1025-38
references.pmid: 16236132
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):4936-42
references.pmid: 15788537
references.citation: Dev Cell. 2005 Feb;8(2):193-202
references.pmid: 15691761
references.citation: Annu Rev Cell Dev Biol. 2004;20:619-47
references.pmid: 15473854
references.citation: PLoS Comput Biol. 2006 May;2(5):e51
references.pmid: 16710449
references.citation: Annu Rev Biophys Biomol Struct. 1998;27:199-224
references.pmid: 9646867
references.citation: PLoS Biol. 2004 Jun;2(6):e123
references.pmid: 15208707
references.citation: Development. 2008 Nov;135(21):3491-9
references.pmid: 18832394
references.citation: Dev Biol. 2000 Oct 1;226(1):34-44
references.pmid: 10993672
references.citation: PLoS Comput Biol. 2007 May;3(5):e92
references.pmid: 17511512
references.citation: Genes Dev. 2006 Feb 15;20(4):429-34
references.pmid: 16481472
references.citation: PLoS One. 2007 May 09;2(5):e434
references.pmid: 17502916
references.citation: Development. 2001 Mar;128(5):617-29
references.pmid: 11171388
references.citation: Nature. 2003 Apr 10;422(6932):633-7
references.pmid: 12687005
references.citation: PLoS Comput Biol. 2007 Feb 2;3(2):e15
references.pmid: 17274682
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2007 May;75(5 Pt 1):051907
references.pmid: 17677098
references.citation: Development. 2006 Feb;133(3):429-37
references.pmid: 16396905
references.citation: Dev Biol. 2009 Dec 15;336(2):156-68
references.pmid: 19782677
references.citation: Bull Math Biol. 2000 Mar;62(2):247-92
references.pmid: 10824430
references.citation: Nature. 2006 Jun 15;441(7095):840-6
references.pmid: 16699522
references.citation: PLoS One. 2007 Aug 22;2(8):e776
references.pmid: 17712424
references.citation: Development. 2002 Feb;129(4):1027-36
references.pmid: 11861485