Robustness under functional constraint: the genetic network for temporal expression in Drosophila neurogenesis.
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.
Nakajima
Akihiko
A
Department of Basic Science, University of Tokyo, Komaba, Tokyo, Japan. nakajima@complex.c.u-tokyo.ac.jp
Isshiki
Takako
T
Kaneko
Kunihiko
K
Ishihara
Shuji
S
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
Dev Dyn. 2005 Mar;232(3):609-16
15704126
J Theor Biol. 2003 Oct 21;224(4):517-37
12957124
J Theor Biol. 2008 May 7;252(1):131-44
18342890
Dev Cell. 2005 Feb;8(2):203-13
15691762
Development. 2008 Sep;135(18):3071-9
18701546
Dev Cell. 2001 Oct;1(4):453-65
11703937
PLoS One. 2008 Jul 23;3(7):e2772
18648662
Cell. 2001 Aug 24;106(4):511-21
11525736
Mol Syst Biol. 2006;2:70
17170765
Genes Dev. 2006 Sep 15;20(18):2618-27
16980589
Nature. 2000 Jul 13;406(6792):188-92
10910359
Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4781-6
15037758
Science. 2005 Sep 23;309(5743):2010-3
16179466
Philos Trans R Soc Lond B Biol Sci. 2008 Jan 12;363(1489):39-56
17309865
Genes Dev. 1998 Jan 15;12(2):246-60
9436984
PLoS Biol. 2004 Sep;2(9):E271
15340490
Genetics. 2004 Aug;167(4):1721-37
15342511
Proc Natl Acad Sci U S A. 2005 Aug 16;102(33):11775-80
16087882
Nature. 1997 Jun 26;387(6636):913-7
9202124
Curr Biol. 2008 Jul 8;18(13):943-50
18571409
PLoS Biol. 2007 Feb;5(2):e37
17298176
PLoS Comput Biol. 2009 Mar;5(3):e1000303
19282965
Development. 1987 Sep;101(1):1-22
2896587
Dev Dyn. 2006 Apr;235(4):861-9
16222713
Genes Cells. 2005 Nov;10(11):1025-38
16236132
Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):4936-42
15788537
Dev Cell. 2005 Feb;8(2):193-202
15691761
Annu Rev Cell Dev Biol. 2004;20:619-47
15473854
PLoS Comput Biol. 2006 May;2(5):e51
16710449
Annu Rev Biophys Biomol Struct. 1998;27:199-224
9646867
PLoS Biol. 2004 Jun;2(6):e123
15208707
Development. 2008 Nov;135(21):3491-9
18832394
Dev Biol. 2000 Oct 1;226(1):34-44
10993672
PLoS Comput Biol. 2007 May;3(5):e92
17511512
Genes Dev. 2006 Feb 15;20(4):429-34
16481472
PLoS One. 2007 May 09;2(5):e434
17502916
Development. 2001 Mar;128(5):617-29
11171388
Nature. 2003 Apr 10;422(6932):633-7
12687005
PLoS Comput Biol. 2007 Feb 2;3(2):e15
17274682
Phys Rev E Stat Nonlin Soft Matter Phys. 2007 May;75(5 Pt 1):051907
17677098
Development. 2006 Feb;133(3):429-37
16396905
Dev Biol. 2009 Dec 15;336(2):156-68
19782677
Bull Math Biol. 2000 Mar;62(2):247-92
10824430
Nature. 2006 Jun 15;441(7095):840-6
16699522
PLoS One. 2007 Aug 22;2(8):e776
17712424
Development. 2002 Feb;129(4):1027-36
11861485