Pre-Steady-State Decoding of the Bicoid Morphogen Gradient

Morphogen gradients are established by the localized production and subsequent diffusion of signaling molecules. It is generally assumed that cell fates are induced only after morphogen profiles have reached their steady state. Yet, patterning processes during early development occur rapidly, and tissue patterning may precede the convergence of the gradient to its steady state. Here we consider the implications of pre-steady-state decoding of the Bicoid morphogen gradient for patterning of the anterior–posterior axis of the Drosophila embryo. Quantitative analysis of the shift in the expression domains of several Bicoid targets (gap genes) upon alteration of bcd dosage, as well as a temporal analysis of a reporter for Bicoid activity, suggest that a transient decoding mechanism is employed in this setting. We show that decoding the pre-steady-state morphogen profile can reduce patterning errors caused by fluctuations in the rate of morphogen production. This can explain the surprisingly small shifts in gap and pair-rule gene expression domains observed in response to alterations in bcd dosage.

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

[2]  R. Schlegel,et al.  Diffusion of injected macromolecules within the cytoplasm of living cells. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[3]  B. Trus,et al.  The cytoplasmic matrix: its volume and surface area and the diffusion of molecules through it. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

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

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

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

[7]  Wolfgang Driever,et al.  Determination of spatial domains of zygotic gene expression in the Drosophila embryo by the affinity of binding sites for the bicoid morphogen , 1989, Nature.

[8]  Diethard Tautz,et al.  Posterior segmentation of the Drosophila embryo in the absence of a maternal posterior organizer gene , 1989, Nature.

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

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

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

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

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

[14]  C. Nüsslein-Volhard,et al.  Rescue of bicoid mutant Drosophila embryos by Bicoid fusion proteins containing heterologous activating sequences , 1989, Nature.

[15]  R. Pepperkok,et al.  Microtubules are stabilized in confluent epithelial cells but not in fibroblasts , 1990, The Journal of cell biology.

[16]  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.

[17]  E. Steingrímsson,et al.  Dual role of the Drosophila pattern gene tailless in embryonic termini. , 1991, Science.

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

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

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

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

[22]  David H. Sharp,et al.  Model for cooperative control of positional information in Drosophila by bicoid and maternal hunchback. , 1995, The Journal of experimental zoology.

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

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

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

[26]  G. Struhl,et al.  Direct and Long-Range Action of a Wingless Morphogen Gradient , 1996, Cell.

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

[28]  G. Struhl,et al.  Direct and Long-Range Action of a DPP Morphogen Gradient , 1996, Cell.

[29]  M. Strigini,et al.  A Hedgehog activity gradient contributes to AP axial patterning of the Drosophila wing. , 1997, Development.

[30]  C. Neumann,et al.  Long-range action of Wingless organizes the dorsal-ventral axis of the Drosophila wing. , 1997, Development.

[31]  M. Jacobs-Lorena,et al.  Developmental Regulation of bicoid mRNA Stability Is Mediated by the First 43 Nucleotides of the 3′ Untranslated Region , 1998, Molecular and Cellular Biology.

[32]  J. Reinitz,et al.  Rapid preparation of a panel of polyclonal antibodies to Drosophila segmentation proteins , 1998, Development Genes and Evolution.

[33]  C. Tickle,et al.  Morphogen gradients in vertebrate limb development. , 1999, Seminars in cell & developmental biology.

[34]  M. Elowitz,et al.  Protein Mobility in the Cytoplasm ofEscherichia coli , 1999, Journal of bacteriology.

[35]  Erik F. Y. Hom,et al.  Diffusion of green fluorescent protein in the aqueous-phase lumen of endoplasmic reticulum. , 1999, Biophysical journal.

[36]  J. Gurdon,et al.  Activin as a morphogen in Xenopus mesoderm induction. , 1999, Seminars in cell & developmental biology.

[37]  Norbert Perrimon,et al.  Negative Feedback Mechanisms and Their Roles during Pattern Formation , 1999, Cell.

[38]  J. Briscoe,et al.  The specification of neuronal identity by graded Sonic Hedgehog signalling. , 1999, Seminars in cell & developmental biology.

[39]  M. Freeman.  Feedback control of intercellular signalling in development , 2000, Nature.

[40]  S. Barolo,et al.  GFP and beta-galactosidase transformation vectors for promoter/enhancer analysis in Drosophila. , 2000, BioTechniques.

[41]  G. Odell,et al.  The segment polarity network is a robust developmental module , 2000, Nature.

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

[43]  M. DePamphilis.  Gene expression at the beginning of animal development , 2002 .

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

[45]  H. Krause,et al.  Anterior-posterior patterning in the Drosophila embryo , 2002 .

[46]  N. Barkai,et al.  Robustness of the BMP morphogen gradient in Drosophila embryonic patterning , 2022 .

[47]  Naama Barkai,et al.  Self-enhanced ligand degradation underlies robustness of morphogen gradients. , 2003, Developmental cell.

[48]  Johannes Jaeger,et al.  Pattern formation and nuclear divisions are uncoupled in Drosophila segmentation: comparison of spatially discrete and continuous models , 2004 .

[49]  Naama Barkai,et al.  Elucidating mechanisms underlying robustness of morphogen gradients. , 2004, Current opinion in genetics & development.

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

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

[52]  Nicholas T Ingolia,et al.  Topology and Robustness in the Drosophila Segment Polarity Network , 2004, PLoS biology.

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

[54]  S. Diekmann,et al.  High- and low-mobility populations of HP1 in heterochromatin of mammalian cells. , 2004, Molecular biology of the cell.

[55]  Qing Nie,et al.  Formation of the BMP activity gradient in the Drosophila embryo. , 2005, Developmental cell.

[56]  W. Bialek,et al.  Diffusion and scaling during early embryonic pattern formation. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[57]  宁北芳,et al.  疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A , 2005 .

[58]  Jeremy L. England,et al.  Morphogen gradient from a noisy source. , 2005, Physical review letters.

[59]  Stanislav Y Shvartsman,et al.  Computational analysis of EGFR inhibition by Argos. , 2005, Developmental biology.

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

[61]  N. Dostatni,et al.  Bicoid Determines Sharp and Precise Target Gene Expression in the Drosophila Embryo , 2005, Current Biology.

[62]  S. Leibler,et al.  Precise domain specification in the developing Drosophila embryo. , 2005, Physical review. E, Statistical, nonlinear, and soft matter physics.

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

[64]  W. Rappel,et al.  Embryonic pattern scaling achieved by oppositely directed morphogen gradients , 2006, Physical biology.

[65]  Krishanu Saha,et al.  Signal dynamics in Sonic hedgehog tissue patterning , 2006, Development.

[66]  C. Aegerter,et al.  Comment on "Precise domain specification in the developing Drosophila embryo". , 2006, Physical review. E, Statistical, nonlinear, and soft matter physics.

[67]  S. Small,et al.  Morphogens: Precise Outputs from a Variable Gradient , 2006, Current Biology.

[68]  David M. Umulis,et al.  Robust, bistable patterning of the dorsal surface of the Drosophila embryo. , 2006, Proceedings of the National Academy of Sciences of the United States of America.