Modeling segmental patterning in Drosophila: Maternal and gap genes.

We propose a new mathematical model describing the establishment of maternal and gap proteins segmental patterning along the antero-posterior axis of the Drosophila early embryo. This model is based on experimental data and, without recurring to pre-defined activation thresholds, predicts qualitatively and quantitatively the expression patterns of the maternal and gap proteins, as well as the expression patterns of proteins resulting from mRNA ectopic expression and from some loss-of-function mutations. We conclude that the gap genes segmental patterning and consequent spatial organization of the embryo is determined by three main factors: (1) the initial positioning of the maternal bicoid and torso mRNA inside the egg, and subsequent diffusion of the corresponding proteins; (2) the structure of the genetic regulatory network; (3) the role of conservation laws in the establishment of steady and non-uniform spatial distributions of non-diffusing proteins.

[1]  T. Kaufman,et al.  Identification and expression of the gap segmentation gene hunchback in Drosophila melanogaster. , 1988, Developmental genetics.

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

[3]  John Reinitz,et al.  Fast redundant dyadic wavelet transform in application to spatial registration of the expression patterns of Drosophila segmentation genes , 2000, Proceedings 15th International Conference on Pattern Recognition. ICPR-2000.

[4]  V. Pirrotta,et al.  The giant gene of Drosophila encodes a b-ZIP DNA-binding protein that regulates the expression of other segmentation gap genes. , 1992, Development.

[5]  E. Steingrímsson,et al.  bicoid and the terminal system activate tailless expression in the early Drosophila embryo. , 1992, Development.

[6]  J. Lengyel,et al.  The zygotic mutant tailless affects the anterior and posterior ectodermal regions of the Drosophila embryo. , 1986, Developmental biology.

[7]  D Kosman,et al.  Concentration-dependent patterning by an ectopic expression domain of the Drosophila gap gene knirps. , 1997, Development.

[8]  H. Meinhardt,et al.  Hierarchical Inductions of Cell States: A Model for Segmentation in Drosophila , 1986, Journal of Cell Science.

[9]  Diethard Tautz,et al.  Finger protein of novel structure encoded by hunchback, a second member of the gap class of Drosophila segmentation genes , 1987, Nature.

[10]  Carlos E Vanario-Alonso,et al.  A kinetic mechanism for Drosophila bicoid cooperative binding. , 2005, Journal of theoretical biology.

[11]  Claude Desplan,et al.  The products of the Drosophila gap genes hunchback and Krüppel bind to the hunchback promoters , 1989, Nature.

[12]  C. Nüsslein-Volhard,et al.  Function of torso in determining the terminal anlagen of the Drosophila embryo , 1988, Nature.

[13]  V. Pirrotta,et al.  Interactions of the Drosophila gap gene giant with maternal and zygotic pattern-forming genes. , 1991, Development.

[14]  J. Posakony,et al.  Posterior stripe expression of hunchback is driven from two promoters by a common enhancer element. , 1995, Development.

[15]  John Reinitz,et al.  Registration of the expression patterns of Drosophila segmentation genes by two independent methods , 2001, Bioinform..

[16]  N. Dostatni,et al.  Persistence of Hunchback in the terminal region of the Drosophila blastoderm embryo impairs anterior development. , 2000, Development.

[17]  H. Jäckle,et al.  Sp1/egr-like zinc-finger protein required for endoderm specification and germ-layer formation in Drosophila , 1994, Nature.

[18]  S. Strickland,et al.  Nanos and pumilio establish embryonic polarity in Drosophila by promoting posterior deadenylation of hunchback mRNA. , 1997, Development.

[19]  Wolfgang Driever,et al.  The bicoid protein is a positive regulator of hunchback transcription in the early Drosophila embryo , 1989, Nature.

[20]  H. Meinhardt,et al.  A model of pattern formation in insect embryogenesis. , 1977, Journal of cell science.

[21]  R. Lehmann,et al.  hunchback, a gene required for segmentation of an anterior and posterior region of the Drosophila embryo. , 1987, Developmental biology.

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

[23]  C. Nüsslein-Volhard,et al.  Organization of anterior pattern in the Drosophila embryo by the maternal gene bicoid , 1986, Nature.

[24]  Alexander M. Samsonov,et al.  How gap genes make their domains: An analytical study based on data driven approximations. , 2001, Chaos.

[25]  David H. Sharp,et al.  Dynamic control of positional information in the early Drosophila embryo , 2004, Nature.

[26]  C. Nüsslein-Volhard Gradients that organize embryo development. , 1996, Scientific American.

[27]  Mike Rothe,et al.  Identical transacting factor requirement for knirps and knirps-related gene expression in the anterior but not in the posterior region of the Drosophila embryo , 1994, Mechanisms of Development.

[28]  H. Jäckle,et al.  Abdominal segmentation of the Drosophila embryo requires a hormone receptor-like protein encoded by the gap gene knirps , 1988, Nature.

[29]  Claude Desplan,et al.  Synergy between the hunchback and bicoid morphogens is required for anterior patterning in Drosophila , 1994, Cell.

[30]  L. Wolpert Positional information and the spatial pattern of cellular differentiation. , 1969, Journal of theoretical biology.

[31]  H. Jäckle,et al.  From gradients to stripes in Drosophila embryogenesis: filling in the gaps. , 1996, Trends in genetics : TIG.

[32]  W. Gehring,et al.  Three maternal coordinate systems cooperate in the patterning of the Drosophila head. , 1994, Development.

[33]  M. Hülskamp,et al.  Gap genes and gradients – The logic behind the gaps , 1991, BioEssays : news and reviews in molecular, cellular and developmental biology.

[34]  M. Levine,et al.  Spatial regulation of the gap gene giant during Drosophila development. , 1991, Development.

[35]  D Kosman,et al.  Automated assay of gene expression at cellular resolution. , 1998, Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing.

[36]  D. Tautz,et al.  Autonomous concentration-dependent activation and repression of Krüppel by hunchback in the Drosophila embryo. , 1994, Development.

[37]  D Bopp,et al.  The role of localization of bicoid RNA in organizing the anterior pattern of the Drosophila embryo. , 1988, The EMBO journal.

[38]  Diethard Tautz,et al.  Regulation of the Drosophila segmentation gene hunchback by two maternal morphogenetic centres , 1988, Nature.

[39]  Ruth Lehmann,et al.  The Drosophila posterior-group gene nanos functions by repressing hunchback activity , 1989, Nature.

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

[41]  T. Bisseling,et al.  Model for the robust establishment of precise proportions in the early Drosophila embryo. , 2004, Journal of theoretical biology.

[42]  G. Struhl,et al.  The torso receptor localizes as well as transduces the spatial signal specifying terminal body pattern in Drosophila , 1993, Nature.

[43]  Norbert Perrimon,et al.  Activation of posterior gap gene expression in the Drosophila blastoderm , 1995, Nature.

[44]  Dierk Niessing,et al.  RNA binding and translational suppression by bicoid , 1996, Nature.

[45]  W. Gehring,et al.  Isolation of caudal, a Drosophila homeo box‐containing gene with maternal expression, whose transcripts form a concentration gradient at the pre‐blastoderm stage , 1985, The EMBO journal.

[46]  David H. Sharp,et al.  Transcriptional Control in Drosophila , 2003, Complexus.

[47]  J. Casanova,et al.  Pattern formation under the control of the terminal system in the Drosophila embryo. , 1990, Development.

[48]  B. Nagorcka A pattern formation mechanism to control spatial organization in the embryo of Drosophila melanogaster. , 1988, Journal of theoretical biology.

[49]  J. Dubnau,et al.  RNA recognition and translational regulation by a homeodomain protein , 1996, Nature.

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

[51]  Peter A. Lawrence,et al.  Control of Drosophila body pattern by the hunchback morphogen gradient , 1992, Cell.

[52]  H. Jäckle,et al.  Gene expression mediated by cis‐acting sequences of the Krüppel gene in response to the Drosophila morphogens bicoid and hunchback. , 1991, The EMBO journal.

[53]  C. Nüsslein-Volhard,et al.  The origin of pattern and polarity in the Drosophila embryo , 1992, Cell.

[54]  S. Kauffman,et al.  Spatial harmonics and pattern specification in early Drosophila development. Part I. Bifurcation sequences and gene expression. , 1990, Journal of theoretical biology.

[55]  E Seifert,et al.  Differential regulation of the two transcripts from the Drosophila gap segmentation gene hunchback. , 1988, The EMBO journal.

[56]  M. Levine,et al.  Mutually repressive interactions between the gap genes giant and Krüppel define middle body regions of the Drosophila embryo. , 1991, Development.

[57]  John Reinitz,et al.  Bicoid cooperative DNA binding is critical for embryonic patterning in Drosophila. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[58]  Lewis Wolpert,et al.  Chapter 6 Positional Information and Pattern Formation , 1971 .

[59]  M Klingler,et al.  Two gap genes mediate maternal terminal pattern information in Drosophila. , 1990, Science.

[60]  R. Lehmann,et al.  The maternal gene nanos has a central role in posterior pattern formation of the Drosophila embryo. , 1991, Development.

[61]  M Hoch,et al.  Competition for overlapping sites in the regulatory region of the Drosophila gene Krüppel. , 1992, Science.

[62]  D. Thieffry,et al.  A logical analysis of the Drosophila gap-gene system. , 2001, Journal of theoretical biology.

[63]  Ruth Lehmann,et al.  Nanos is the localized posterior determinant in Drosophila , 1991, Cell.

[64]  A. Turing The chemical basis of morphogenesis , 1952, Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences.

[65]  R. Lehmann,et al.  Drosophila nurse cells produce a posterior signal required for embryonic segmentation and polarity , 1988, Nature.

[66]  T. Lacalli Modeling the Drosophila pair-rule pattern by reaction-diffusion: gap input and pattern control in a 4-morphogen system. , 1990, Journal of theoretical biology.

[67]  K. Struhl,et al.  The gradient morphogen bicoid is a concentration-dependent transcriptional activator , 1989, Cell.

[68]  B C Goodwin,et al.  Drosophila segmentation: supercomputer simulation of prepattern hierarchy. , 1990, Journal of theoretical biology.

[69]  Daniel St Johnston,et al.  staufen, a gene required to localize maternal RNAs in the Drosophila egg , 1991, Cell.

[70]  D. Tautz,et al.  Zygotic caudal regulation by hunchback and its role in abdominal segment formation of the Drosophila embryo. , 1995, Development.

[71]  David H. Sharp,et al.  Dynamical Analysis of Regulatory Interactions in the Gap Gene System of Drosophila melanogaster , 2004, Genetics.

[72]  R. Dilão,et al.  A simple framework to describe the regulation of gene expression in prokaryotes. , 2005, Comptes rendus biologies.

[73]  G. Struhl,et al.  Localized surface activity of torso, a receptor tyrosine kinase, specifies terminal body pattern in Drosophila. , 1989, Genes & development.

[74]  M. Levine,et al.  Control of the initiation of homeotic gene expression by the gap genes giant and tailless in Drosophila. , 1990, Developmental biology.

[75]  G. Struhl,et al.  Differing strategies for organizing anterior and posterior body pattern in Drosophila embryos , 1989, Nature.

[76]  Marek Mlodzik,et al.  Expression of the caudal gene in the germ line of Drosophila: Formation of an RNA and protein gradient during early embryogenesis , 1987, Cell.

[77]  Diethard Tautz,et al.  A morphogenetic gradient of hunchback protein organizes the expression of the gap genes Krüppel and knirps in the early Drosophila embryo , 1990, Nature.

[78]  H. Meinhardt,et al.  A theory of biological pattern formation , 1972, Kybernetik.

[79]  John Reinitz,et al.  Spatio-Temporal Registration of the Expression Patterns of Drosophila Segmentation Genes , 1999, ISMB.

[80]  M Hoch,et al.  Spatial control of the gap gene knirps in the Drosophila embryo by posterior morphogen system. , 1992, Science.

[81]  H. Jäckle,et al.  Control and function of terminal gap gene activity in the posterior pole region of the Drosophila embryo , 1991, Mechanisms of Development.

[82]  M. Bate,et al.  The development of Drosophila melanogaster , 1993 .

[83]  M. Akam,et al.  The molecular basis for metameric pattern in the Drosophila embryo. , 1987, Development.

[84]  Hans Meinhardt,et al.  Biological Pattern Formation as a Complex Dynamic Phenomenon , 1997 .

[85]  R. Dilão The reaction-diffusion approach to morphogenesis , 2005, q-bio/0502041.

[86]  V. Pirrotta,et al.  A novel spatial transcription pattern associated with the segmentation gene, giant, of Drosophila. , 1989, The EMBO journal.

[87]  H. Meinhardt,et al.  Pattern formation by local self-activation and lateral inhibition. , 2000, BioEssays : news and reviews in molecular, cellular and developmental biology.

[88]  H. Jäckle,et al.  Krüppel requirement for knirps enhancement reflects overlapping gap gene activities in the Drosophila embryo , 1989, Nature.

[89]  C. Nüsslein-Volhard,et al.  Krüppel, a gene whose activity is required early in the zygotic genome for normal embryonic segmentation. , 1984, Developmental biology.

[90]  A. Gierer Generation of biological patterns and form: some physical, mathematical, and logical aspects. , 1981, Progress in biophysics and molecular biology.

[91]  Michael J. Pankratz,et al.  Gradients of Krüppel and knirps gene products direct pair-rule gene stripe patterning in the posterior region of the drosophila embryo , 1990, Cell.

[92]  H. Jäckle,et al.  Spatial and temporal patterns of Krüppel gene expression in early Drosophila embryos , 1985, Nature.

[93]  Sandeep Krishna,et al.  Stochastic simulations of the origins and implications of long-tailed distributions in gene expression. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[94]  J. Lengyel,et al.  Control of tailless expression by bicoid, dorsal and synergistically interacting terminal system regulatory elements , 1993, Mechanisms of Development.

[95]  Robert J. Diaz,et al.  The Drosophila gene tailless is expressed at the embryonic termini and is a member of the steroid receptor superfamily , 1990, Cell.

[96]  G. Struhl,et al.  A molecular gradient in early Drosophila embryos and its role in specifying the body pattern , 1986, Nature.