Filtering transcriptional noise during development: concepts and mechanisms

The assignation of cell fates during eukaryotic development relies on the coordinated and stable expression of cohorts of genes within cell populations. The precise and reproducible nature of this process is remarkable given that, at the single-cell level, the transcription of individual genes is associated with noise — random molecular fluctuations that create variability in the levels of gene expression within a cell population. Here we consider the implications of transcriptional noise for development and suggest the existence of molecular devices that are dedicated to filtering noise. On the basis of existing evidence, we propose that one such mechanism might depend on the Wnt signalling pathway.

[1]  Andrew P McMahon,et al.  A mitogen gradient of dorsal midline Wnts organizes growth in the CNS. , 2002, Development.

[2]  J. Ferrell Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability. , 2002, Current opinion in cell biology.

[3]  S. Leibler,et al.  Establishment of developmental precision and proportions in the early Drosophila embryo , 2002, Nature.

[4]  Randall T Moon,et al.  A second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling. , 2003, Developmental cell.

[5]  Lewis Wolpert,et al.  Principles of Development , 1997 .

[6]  G. Odell,et al.  Robustness, Flexibility, and the Role of Lateral Inhibition in the Neurogenic Network , 2002, Current Biology.

[7]  S. Shen-Orr,et al.  Network motifs: simple building blocks of complex networks. , 2002, Science.

[8]  Mads Kærn,et al.  Noise in eukaryotic gene expression , 2003, Nature.

[9]  J. Gurdon,et al.  A community effect in animal development , 1988, Nature.

[10]  P. Maini,et al.  Pattern formation by lateral inhibition with feedback: a mathematical model of delta-notch intercellular signalling. , 1996, Journal of theoretical biology.

[11]  Christian Wehrle,et al.  Wnt3a plays a major role in the segmentation clock controlling somitogenesis. , 2003, Developmental cell.

[12]  C. Nüsslein-Volhard,et al.  A gradient of bicoid protein in Drosophila embryos , 1988, Cell.

[13]  J Galceran,et al.  Rescue of a Wnt mutation by an activated form of LEF-1: Regulation of maintenance but not initiation of Brachyury expression , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[14]  T. Klein,et al.  The vestigial gene product provides a molecular context for the interpretation of signals during the development of the wing in Drosophila. , 1999, Development.

[15]  J. Gurdon,et al.  A community effect in muscle development , 1993, Current Biology.

[16]  J. Modolell,et al.  Different contributions of pannier and wingless to the patterning of the dorsal mesothorax of Drosophila. , 1999, Development.

[17]  S. Cohen,et al.  Problems and paradigms: Morphogens and pattern formation , 1997 .

[18]  Alfonso Martinez Arias,et al.  Armadillo/β-catenin-dependent Wnt signalling is required for the polarisation of epidermal cells during dorsal closure in Drosophila , 2004, Development.

[19]  H. Clevers,et al.  Wnt signalling in stem cells and cancer , 2005, Nature.

[20]  Xi C. He,et al.  Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierarchically controlled during early hematopoiesis. , 2003, Blood.

[21]  N. Perrimon,et al.  Functional Genomic Analysis of the Wnt-Wingless Signaling Pathway , 2005, Science.

[22]  Scott Barolo,et al.  Three habits of highly effective signaling pathways: principles of transcriptional control by developmental cell signaling. , 2002, Genes & development.

[23]  Xi He,et al.  Coactivation of Rac and Rho by Wnt/Frizzled signaling is required for vertebrate gastrulation. , 2003, Genes & development.

[24]  David M. Holloway,et al.  Making the body plan: Precision in the genetic hierarchy of Drosophila embryo segmentation , 2003, Silico Biol..

[25]  Anjen Chenn,et al.  Regulation of Cerebral Cortical Size by Control of Cell Cycle Exit in Neural Precursors , 2002, Science.

[26]  Julian Lewis Autoinhibition with Transcriptional Delay A Simple Mechanism for the Zebrafish Somitogenesis Oscillator , 2003, Current Biology.

[27]  N. Perrimon,et al.  Notch modulates Wnt signalling by associating with Armadillo/β-catenin and regulating its transcriptional activity , 2005, Development.

[28]  Keith Brennan,et al.  CSL-independent Notch signalling: a checkpoint in cell fate decisions during development? , 2002, Current opinion in genetics & development.

[29]  K. Sachs,et al.  Causal Protein-Signaling Networks Derived from Multiparameter Single-Cell Data , 2005, Science.

[30]  Alfonso Martinez Arias,et al.  Molecular Principles of Animal Development , 2002 .

[31]  Jeffrey D. Axelrod,et al.  A Second Canon , 2003 .

[32]  R. Tjian,et al.  Transcription regulation and animal diversity , 2003, Nature.

[33]  R. Milo,et al.  Network motifs in integrated cellular networks of transcription-regulation and protein-protein interaction. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[34]  L. Hood,et al.  A Genomic Regulatory Network for Development , 2002, Science.

[35]  L. Hood,et al.  Regulatory gene networks and the properties of the developmental process , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[36]  G. Schubiger,et al.  Transdetermination in Drosophila imaginal discs: a model for understanding pluripotency and selector gene maintenance. , 2003, Current opinion in genetics & development.

[37]  Rustem F. Ismagilov,et al.  Dynamics of Drosophila embryonic patterning network perturbed in space and time using microfluidics , 2005, Nature.

[38]  Hans Clevers,et al.  Caught up in a Wnt storm: Wnt signaling in cancer. , 2003, Biochimica et biophysica acta.

[39]  Robert Geisler,et al.  Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation , 2000, Nature.

[40]  Michael Levine,et al.  Whole-genome analysis of Drosophila gastrulation. , 2004, Current opinion in genetics & development.

[41]  B. de Strooper,et al.  Analysis of Notch function in presomitic mesoderm suggests a gamma-secretase-independent role for presenilins in somite differentiation. , 2005, Developmental cell.

[42]  J. Paulsson Summing up the noise in gene networks , 2004, Nature.

[43]  D. Mccormick Sequence the Human Genome , 1986, Bio/Technology.

[44]  C. Pesce,et al.  Regulated cell-to-cell variation in a cell-fate decision system , 2005, Nature.

[45]  R. Moon,et al.  The Wnt/Ca2+ pathway: a new vertebrate Wnt signaling pathway takes shape. , 2000, Trends in genetics : TIG.

[46]  J. Gurdon,et al.  eFGF and its mode of action in the community effect during Xenopus myogenesis. , 2001, Development.

[47]  Nicola J. Rinaldi,et al.  Transcriptional Regulatory Networks in Saccharomyces cerevisiae , 2002, Science.

[48]  S Cohen,et al.  Morphogens and pattern formation. , 1997, BioEssays : news and reviews in molecular, cellular and developmental biology.

[49]  Judith A. Kassis,et al.  Two-tiered regulation of spatially patterned engrailed gene expression during Drosophila embryogenesis , 1988, Nature.

[50]  C. Nüsslein-Volhard,et al.  The bicoid protein determines position in the Drosophila embryo in a concentration-dependent manner , 1988, Cell.

[51]  Farren J. Isaacs,et al.  Prediction and measurement of an autoregulatory genetic module , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[52]  Alfonso Martinez Arias,et al.  Repression by Notch is required before Wingless signalling during muscle progenitor cell development in Drosophila , 1999, Current Biology.

[53]  P. Swain,et al.  Gene Regulation at the Single-Cell Level , 2005, Science.

[54]  A. Martinez Arias,et al.  The Informational Content of Gradients of Wnt Proteins , 2000, Science's STKE.

[55]  S. Shen-Orr,et al.  Network motifs in the transcriptional regulation network of Escherichia coli , 2002, Nature Genetics.

[56]  K. White,et al.  Patterns of Gene Expression During Drosophila Mesoderm Development , 2001, Science.

[57]  S. Fiering,et al.  To be or not to be active: the stochastic nature of enhancer action. , 2000, BioEssays : news and reviews in molecular, cellular and developmental biology.

[58]  Farren J. Isaacs,et al.  Signal Processing in Single Cells , 2005, Science.

[59]  M. Greaves,et al.  Multilineage gene expression precedes commitment in the hemopoietic system. , 1997, Genes & development.

[60]  E. Davidson,et al.  Gene regulatory networks for development. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[61]  F. Schweisguth,et al.  Regulation of Notch Signaling Activity , 2004, Current Biology.

[62]  J. V. Moran,et al.  Initial sequencing and analysis of the human genome. , 2001, Nature.

[63]  S Wan,et al.  Multiple signalling pathways establish cell fate and cell number in Drosophila malpighian tubules. , 2000, Developmental biology.

[64]  B. van Steensel,et al.  Mapping of genetic and epigenetic regulatory networks using microarrays. , 2005, Nature genetics.

[65]  A. Martinez Arias,et al.  Roles of wingless in patterning the larval epidermis of Drosophila. , 1991, Development.

[66]  E. Davidson,et al.  Modeling transcriptional regulatory networks. , 2002, BioEssays : news and reviews in molecular, cellular and developmental biology.

[67]  J. Raser,et al.  Control of Stochasticity in Eukaryotic Gene Expression , 2004, Science.

[68]  Sudhir Kumar,et al.  Comparative Genomics in Eukaryotes , 2005 .

[69]  Elaine Fuchs,et al.  Defining the impact of beta-catenin/Tcf transactivation on epithelial stem cells. , 2005, Genes & development.

[70]  C. Rao,et al.  Control, exploitation and tolerance of intracellular noise , 2002, Nature.

[71]  J. Treisman,et al.  Osa-containing Brahma chromatin remodeling complexes are required for the repression of wingless target genes. , 2000, Genes & development.

[72]  M. Baylies,et al.  Specification of individual Slouch muscle progenitors in Drosophila requires sequential Wingless signaling , 2005, Development.

[73]  M. Ptashne A genetic switch : phage λ and higher organisms , 1992 .

[74]  A. Martinez Arias,et al.  Wnts as morphogens? The view from the wing of Drosophila , 2003, Nature reviews. Molecular cell biology.

[75]  J. Gergen,et al.  Distinct in vivo requirements for establishment versus maintenance of transcriptional repression , 2002, Nature Genetics.

[76]  Jonathan M Irish,et al.  Single Cell Profiling of Potentiated Phospho-Protein Networks in Cancer Cells , 2004, Cell.

[77]  Daniel St Johnston,et al.  Seeing Is Believing The Bicoid Morphogen Gradient Matures , 2004, Cell.

[78]  A. van Oudenaarden,et al.  Noise Propagation in Gene Networks , 2005, Science.

[79]  J. Whangbo,et al.  A Wnt signaling system that specifies two patterns of cell migration in C. elegans. , 1999, Molecular cell.

[80]  M Laurent,et al.  Multistability: a major means of differentiation and evolution in biological systems. , 1999, Trends in biochemical sciences.

[81]  Carmen Birchmeier,et al.  beta-Catenin signals regulate cell growth and the balance between progenitor cell expansion and differentiation in the nervous system. , 2003, Developmental biology.

[82]  E. Davidson Genomic Regulatory Systems: Development and Evolution , 2005 .

[83]  N E Baker,et al.  Role of segment polarity genes in the definition and maintenance of cell states in the Drosophila embryo. , 1988, Development.

[84]  M. Elowitz,et al.  Combinatorial Synthesis of Genetic Networks , 2002, Science.

[85]  M. Gerstein,et al.  Structure and evolution of transcriptional regulatory networks. , 2004, Current opinion in structural biology.

[86]  R. Nusse,et al.  The Wnt signaling pathway in development and disease. , 2004, Annual review of cell and developmental biology.

[87]  A. Oudenaarden,et al.  Enhancement of cellular memory by reducing stochastic transitions , 2005, Nature.

[88]  Elaine Fuchs,et al.  Defining the impact of (cid:1) -catenin/Tcf transactivation on epithelial stem cells , 2005 .

[89]  P. Swain,et al.  Stochastic Gene Expression in a Single Cell , 2002, Science.

[90]  R. Weiss,et al.  Ultrasensitivity and noise propagation in a synthetic transcriptional cascade. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[91]  M. Groudine,et al.  Enhancers increase the probability but not the level of gene expression. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[92]  T. Elston,et al.  Stochasticity in gene expression: from theories to phenotypes , 2005, Nature Reviews Genetics.

[93]  M. Bate,et al.  wingless is required for the formation of a subset of muscle founder cells during Drosophila embryogenesis. , 1995, Development.