Noise transmission during the dynamic pattern formation in fly embryos

Abstract

Background: Developmental patterning is highly reproducible and accurate at the single-cell level during fly embryogenesis despite the gene expression noise and external perturbations such as the variation of the embryo length, temperature and genes. To reveal the underlying mechanism, it is very important to characterize the noise transmission during the dynamic pattern formation. Two hypotheses have been proposed. The “channel” scenario requires a highly reproducible input and an accurate interpretation by downstream genes. In contrast, the “filter” scenario proposes a noisy input and a noise filter via the cross-regulation of the downstream network. It has been under great debates which scenario the fly embryogenesis follows.

Results: The first 3-h developmental patterning of fly embryos is orchestrated by a hierarchical segmentation gene network, which rewires upon the maternal to zygotic transition. Starting from the highly reproducible maternal gradients, the positional information is refined to the single-cell precision through the highly dynamical evolved zygotic gene expression profiles. Thus the fly embryo development might strictly fit into neither the originally proposed “filter” nor “channel” scenario. The controversy that which scenario the fly embryogenesis follows could be further clarified by combining quantitative measurements and modeling.

Conclusions: Fly embryos have become one of the perfect model systems for quantitative systems biology studies. The underlying mechanism discovered from fly embryogenesis will deepen our understanding of the noise control of the gene network, facilitate searching for more efficient and safer methods for cell programming and reprogramming, and have the great potential for tissue engineering and regenerative medicine.

Graphical abstract

Keywords

pattern formation / gene regulatory network / noise / embryogenesis / Drosophila

References

[1] Gregor, T., Tank, D. W., Wieschaus, E. F. and Bialek, W. (2007) Probing the limits to positional information. Cell, 130, 153–164

[2] Gregor, T., Wieschaus, E. F., McGregor, A. P., Bialek, W. and Tank, D. W. (2007) Stability and nuclear dynamics of the Bicoid morphogen gradient. Cell, 130, 141–152

[3] Namba, R., Pazdera, T. M., Cerrone, R. L. and Minden, J. S. (1997) Drosophila embryonic pattern repair: how embryos respond to bicoid dosage alteration. Development, 124, 1393–1403

[4] Vincent, A., Blankenship, J. T. and Wieschaus, E. (1997) Integration of the head and trunk segmentation systems controls cephalic furrow formation in Drosophila. Development, 124, 3747–3754

[5] Liu, F., Morrison, A. H. and Gregor, T. (2013) Dynamic interpretation of maternal inputs by the Drosophila segmentation gene network. Proc. Natl. Acad. Sci. USA, 110, 6724–6729

[6] Eldar, A. and Elowitz, M. B. (2010) Functional roles for noise in genetic circuits. Nature, 467, 167–173

[7] Elowitz, M. B., Levine, A. J., Siggia, E. D. and Swain, P. S. (2002) Stochastic gene expression in a single cell. Science, 297, 1183–1186

[8] Ghodsi, Z., Hassani, H. and McGhee, K. (2015) Mathematical approaches in studying bicoid gene. Quant. Biol., 3, 182–192

[9] Gregor, T., Garcia, H. G. and Little, S. C. (2014) The embryo as a laboratory: quantifying transcription in Drosophila. Trends Genet., 30, 364–375

[10] Rogers, K. W. and Schier, A. F. (2011) Morphogen gradients: from generation to interpretation. Annu. Rev. Cell Dev. Biol., 27, 377–407

[11] Porcher, A. and Dostatni, N. (2010) The bicoid morphogen system. Curr. Biol., 20, R249–R254

[12] Jaeger, J. (2011) The gap gene network. Cell. Mol. Life Sci., 68, 243–274

[13] Jaeger, J. (2009) Modelling the Drosophila embryo. Mol. Biosyst., 5, 1549–1568

[14] Farrell, J. A. and O’Farrell, P. H. (2014) From egg to gastrula: how the cell cycle is remodeled during the Drosophila mid-blastula transition. Annu. Rev. Genet., 48, 269–294

[15] Driever, W. and Nüsslein-Volhard, C. (1988) A gradient of bicoid protein in Drosophila embryos. Cell, 54, 83–93

[16] Driever, W. and Nüsslein-Volhard, C. (1988) The bicoid protein determines position in the Drosophila embryo in a concentration-dependent manner. Cell, 54, 95–104

[17] Irish, V., Lehmann, R. and Akam, M. (1989) The Drosophila posterior-group gene nanos functions by repressing hunchback activity. Nature, 338, 646–648

[18] Dubuis, J. O., Samanta, R. and Gregor, T. (2013) Accurate measurements of dynamics and reproducibility in small genetic networks. Mol. Syst. Biol., 9, 639

[19] Surkova, S., Myasnikova, E., Kozlov, K. N., Pisarev, A., Reinitz, J. and Samsonova, M. (2013) Quantitative imaging of gene expression in Drosophila embryos. Cold Spring Harb. Protoc., 2013, 488–497

[20] Little, S. C., Tkačik, G., Kneeland, T. B., Wieschaus, E. F. and Gregor, T. (2011) The formation of the Bicoid morphogen gradient requires protein movement from anteriorly localized mRNA. PLoS Biol., 9, e1000596

[21] Grimm, O., Coppey, M. and Wieschaus, E. (2010) Modelling the Bicoid gradient. Development, 137, 2253–2264

[22] Berezhkovskii, A. M., Sample, C. and Shvartsman, S. Y. (2010) How long does it take to establish a morphogen gradient? Biophys. J., 99, L59–L61

[23] Drocco, J. A., Grimm, O., Tank, D. W. and Wieschaus, E. (2011) Measurement and perturbation of morphogen lifetime: effects on gradient shape. Biophys. J., 101, 1807–1815

[24] Liu, J., He, F. and Ma, J. (2011) Morphogen gradient formation and action: insights from studying Bicoid protein degradation. Fly (Austin), 5, 242–246

[25] Abu-Arish, A., Porcher, A., Czerwonka, A., Dostatni, N. and Fradin, C. (2010) High mobility of bicoid captured by fluorescence correlation spectroscopy: implication for the rapid establishment of its gradient. Biophys. J., 99, L33–L35

[26] Liu, J. and Ma, J. (2013) Uncovering a dynamic feature of the transcriptional regulatory network for anterior–posterior patterning in the Drosophila embryo. PLoS One, 8, e62641

[27] Margolis, J. S., Borowsky, M. L., Steingrímsson, E., Shim, C. W., Lengyel, J. A. and Posakony, J. W. (1995) Posterior stripe expression of hunchback is driven from two promoters by a common enhancer element. Development, 121, 3067–3077

[28] Lopes, F. J., Vieira, F. M., Holloway, D. M., Bisch, P. M. and Spirov, A. V. (2008) Spatial bistability generates hunchback expression sharpness in the Drosophila embryo. PLoS Comput. Biol., 4, e1000184

[29] Hülskamp, M., Lukowitz, W., Beermann, A., Glaser, G. and Tautz, D. (1994) Differential regulation of target genes by different alleles of the segmentation gene hunchback in Drosophila. Genetics, 138, 125–134

[30] Schröder, C., Tautz, D., Seifert, E. and Jäckle, H. (1988) Differential regulation of the two transcripts from the Drosophila gap segmentation gene hunchback. EMBO J., 7, 2881–2887

[31] Perry, M. W., Bothma, J. P., Luu, R. D. and Levine, M. (2012) Precision of hunchback expression in the Drosophila embryo. Curr. Biol., 22, 2247–2252

[32] Surkova, S., Golubkova, E., Manu, L., Panok, L., Mamon, J., Reinitz, M. and Samsonova (2013) Quantitative dynamics and increased variability of segmentation gene expression in the Drosophila Krüppel and knirps mutants. Dev. Biol., 376, 99–112

[33] Perry, M. W., Boettiger, A. N. and Levine, M. (2011) Multiple enhancers ensure precision of gap gene-expression patterns in the Drosophila embryo. Proc. Natl. Acad. Sci. USA, 108, 13570–13575

[34] Lehmann, R. and Nüsslein-Volhard, C. (1987) hunchback, a gene required for segmentation of an anterior and posterior region of the Drosophila embryo. Dev. Biol., 119, 402–417

[35] Petkova, M. D., Tkačik, G., Bialek, W., Wieschaus, E. F. and Gregor, T. (2016) Optimal decoding of information from a genetic network.

[36] Petkova, M. D., Little, S. C., Liu, F. and Gregor, T. (2014) Maternal origins of developmental reproducibility. Curr. Biol., 24, 1283–1288

[37] Wolpert, L. (1969) Positional information and the spatial pattern of cellular differentiation. J. Theor. Biol., 25, 1–47

[38] He, F., Wen, Y., Deng, J., Lin, X., Lu, L. J., Jiao, R. and Ma, J. (2008) Probing intrinsic properties of a robust morphogen gradient in Drosophila. Dev. Cell, 15, 558–567

[39] Houchmandzadeh, B., Wieschaus, E. and Leibler, S. (2002) Establishment of developmental precision and proportions in the early Drosophila embryo. Nature, 415, 798–802

[40] Jaeger, J., Surkova, S., Blagov, M., Janssens, H., Kosman, D., Kozlov, K. N., Manu, E., Myasnikova, C. E., Vanario-Alonso, M., Samsonova, M, (2004) Dynamic control of positional information in the early Drosophila embryo. Nature, 430, 368–371

[41] Manu, Surkova, S., Spirov, A. V., Gursky, V. V., Janssens, H., Kim, A. R., Radulescu, O., Vanario-Alonso, C. E., Sharp, D. H., Samsonova, M., (2009) Canalization of gene expression in the Drosophila blastoderm by gap gene cross regulation. PLoS Biol., 7, e1000049

[42] Green, J. B. and Sharpe, J. (2015) Positional information and reaction-diffusion: two big ideas in developmental biology combine. Development, 142, 1203–1211

[43] Turing, A. M. (1952) The chemical basis of morphogenesis. Philosoph. Trans. Royal Soc. London, 237,37–72

[44] Gregor, T., Bialek, W., de Ruyter van Steveninck, R. R., Tank, D. W. and Wieschaus, E. F. (2005) Diffusion and scaling during early embryonic pattern formation. Proc. Natl. Acad. Sci. USA, 102, 18403–18407

[45] Grimm, O. and Wieschaus, E. (2010) The Bicoid gradient is shaped independently of nuclei. Development, 137, 2857–2862

[46] Cheung, D., Miles, C., Kreitman, M. and Ma, J. (2011) Scaling of the Bicoid morphogen gradient by a volume-dependent production rate. Development, 138, 2741–2749

[47] He, F., Wei, C., Wu, H., Cheung, D., Jiao, R. and Ma, J. (2015) Fundamental origins and limits for scaling a maternal morphogen gradient. Nat. Commun., 6, 6679

[48] de Lachapelle, A. M. and Bergmann, S. (2010) Precision and scaling in morphogen gradient read-out. Mol. Syst. Biol., 6, 351

[49] Bergmann, S., Sandler, O., Sberro, H., Shnider, S., Schejter, E., Shilo, B.-Z. and Barkai, N. (2007) Pre-steady-state decoding of the Bicoid morphogen gradient. PLoS Biol., 5, e46

[50] Jaeger, J. (2010) A matter of timing and precision. Mol. Syst. Biol., 6, 427

[51] Houchmandzadeh, B., Wieschaus, E. and Leibler, S. (2005) Precise domain specification in the developing Drosophila embryo. Phys. Rev. E Stat. Nonlin. Soft Matter Phys., 72, 061920

[52] Howard, M. and ten Wolde, P. R. (2005) Finding the center reliably: robust patterns of developmental gene expression. Phys. Rev. Lett., 95, 208103

[53] Cheung, D. and Ma, J. (2015) Probing the impact of temperature on molecular events in a developmental system. Sci. Rep., 5, 13124

[54] Kuntz, S. G. and Eisen, M. B. (2014) Drosophila embryogenesis scales uniformly across temperature in developmentally diverse species. PLoS Genet., 10, e1004293

[55] Lucchetta, E. M., Lee, J. H., Fu, L. A., Patel, N. H. and Ismagilov, R. F. (2005) Dynamics of Drosophila embryonic patterning network perturbed in space and time using microfluidics. Nature, 434, 1134–1138

[56] Lucchetta, E. M., Vincent, M. E. and Ismagilov, R. F. (2008) A precise Bicoid gradient is nonessential during cycles 11–13 for precise patterning in the Drosophila blastoderm. PLoS One, 3, e3651

[57] Lucchetta, E. M., Carthew, R. W. and Ismagilov, R. F. (2009) The endo-siRNA pathway is essential for robust development of the Drosophila embryo. PLoS One, 4, e7576

[58] Crauk, O. and Dostatni, N. (2005) Bicoid determines sharp and precise target gene expression in the Drosophila embryo. Curr. Biol., 15, 1888–1898

[59] Kugler, J.-M. and Lasko, P. (2009) Localization, anchoring and translational control of oskar, gurken, bicoid and nanos mRNA during Drosophila oogenesis. Fly (Austin), 3, 15–28

[60] Aegerter-Wilmsen, T., Aegerter, C. M. and Bisseling, T. (2005) Model for the robust establishment of precise proportions in the early Drosophila embryo. J. Theor. Biol., 234, 13–19

[61] Garcia, H. G., Tikhonov, M., Lin, A. and Gregor, T. (2013) Quantitative imaging of transcription in living Drosophila embryos links polymerase activity to patterning. Curr. Biol., 23, 2140–2145

[62] Lucas, T., Ferraro, T., Roelens, B., De Las Heras Chanes, J., Walczak, A. M., Coppey, M. and Dostatni, N. (2013) Live imaging of bicoid-dependent transcription in Drosophila embryos. Curr. Biol., 23, 2135–2139

[63] Xu, H., Sepúlveda, L. A., Figard, L., Sokac, A. M. and Golding, I. (2015) Combining protein and mRNA quantification to decipher transcriptional regulation. Nat. Methods, 12, 739–742

[64] Little, S. C., Tikhonov, M. and Gregor, T. (2013) Precise developmental gene expression arises from globally stochastic transcriptional activity. Cell, 154, 789–800

[65] Garcia, H. G., Tikhonov, M., Lin, A. and Gregor, T. (2013) Quantitative imaging of transcription in living Drosophila embryos links polymerase activity to patterning. Curr. Biol., 23, 2140– 2145

[66] Golding, I., Paulsson, J., Zawilski, S. M. and Cox, E. C. (2005) Real-time kinetics of gene activity in individual bacteria. Cell, 123, 1025–1036

[67] Reeves, G. T., Trisnadi, N., Truong, T. V., Nahmad, M., Katz, S. and Stathopoulos, A. (2012) Dorsal-ventral gene expression in the Drosophila embryo reflects the dynamics and precision of the dorsal nuclear gradient. Dev. Cell, 22, 544–557

[68] Giepmans, B. N., Adams, S. R., Ellisman, M. H., Tsien, R. Y(2006) The fluorescent toolbox for assessing protein location and function. Science, 312, 217–224

[69] Myasnikova, E., Samsonova, A., Kozlov, K., Samsonova, M. and Reinitz, J. (2001) Registration of the expression patterns of Drosophila segmentation genes by two independent methods. Bioinformatics, 17, 3–12

[70] Blythe, S. A. and Wieschaus, E. F. (2016) Establishment and maintenance of heritable chromatin structure during early Drosophila embryogenesis. eLife, 5, 5

[71] Fowlkes, C. C., Hendriks, C. L. L., Keränen, S. V., Weber, G. H., Rübel, O., Huang, M.-Y., Chatoor, S., DePace, A. H., Simirenko, L., Henriquez, C., (2008) A quantitative spatiotemporal atlas of gene expression in the Drosophila blastoderm. Cell, 133, 364–374

[72] Surkova, S., Kosman, D., Kozlov, K., Manu, E., Myasnikova, A. A., Samsonova, A., Spirov, C. E., Vanario-Alonso, M., Samsonova, J. and Reinitz (2008) Characterization of the Drosophila segment determination morphome. Dev. Biol., 313, 844–862

[73] Barrangou, R. (2014) RNA events. Cas9 targeting and the CRISPR revolution. Science, 344, 707–708

[74] Bassett, A. R. and Liu, J.-L. (2014) CRISPR/Cas9 and genome editing in Drosophila. J. Genet. Genomics, 41, 7–19

[75] Papatsenko, D. and Levine, M. (2011) The Drosophila gap gene network is composed of two parallel toggle switches. PLoS One, 6, e21145

[76] Bertrand, E., Chartrand, P., Schaefer, M., Shenoy, S. M., Singer, R. H. and Long, R. M. (1998) Localization of ASH1 mRNA particles in living yeast. Mol. Cell, 2, 437–445

[77] Bothma, J. P., Garcia, H. G., Esposito, E., Schlissel, G., Gregor, T. and Levine, M. (2014) Dynamic regulation of eve stripe 2 expression reveals transcriptional bursts in living Drosophila embryos. Proc. Natl. Acad. Sci. USA, 111, 10598–10603

[78] Keller, P. J. (2013) Imaging morphogenesis: technological advances and biological insights. Science, 340, 1234168

[79] Stegmaier, J., Amat, F., Lemon, W. C., McDole, K., Wan, Y., Teodoro, G., Mikut, R. and Keller, P. J. (2016) Real-time three-dimensional cell segmentation in large-scale microscopy data of developing embryos. Dev. Cell, 36, 225–240

[80] Ji, N., Milkie, D. E. and Betzig, E. (2010) Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues. Nat. Methods, 7, 141–147

[81] Huang, A., Amourda, C., Zhang, S., Tolwinski, N. S., and Saunders, T. E. (2017) Decoding temporal interpretation of the morphogen Bicoid in the early Drosophila embryo. eLife, 6, e26258

[82] Perry, M. W., Boettiger, A. N., Bothma, J. P. and Levine, M. (2010) Shadow enhancers foster robustness of Drosophila gastrulation. Curr. Biol., 20, 1562–1567

[83] El-Sherif, E. and Levine, M. (2016) Shadow enhancers mediate dynamic shifts of gap gene expression in the Drosophila embryo. Curr. Biol., 26, 1164–1169

[84] Lagha, M., Bothma, J. P., Esposito, E., Ng, S., Stefanik, L., Tsui, C., Johnston, J., Chen, K., Gilmour, D. S., Zeitlinger, J., (2013) Paused Pol II coordinates tissue morphogenesis in the Drosophila embryo. Cell, 153, 976–987

[85] Liu, J. and Ma, J. (2011) Fates-shifted is an F-box protein that targets Bicoid for degradation and regulates developmental fate determination in Drosophila embryos. Nat. Cell Biol., 13, 22–29

[86] Liu, J., Xiao, Y., Zhang, T. and Ma, J. (2016) Time to move on: modeling transcription dynamics during an embryonic transition away from maternal control. Fly (Austin), 10, 101–107

[87] Liu, J. and Ma, J. (2015) Modulation of temporal dynamics of gene transcription by activator potency in the Drosophila embryo. Development, 142, 3781–3790

[88] Phillips, R. (2015) Theory in biology: Figure 1 or Figure 7? Trends Cell Biol., 25, 723–729

[89] Estrada, J., Wong, F., DePace, A. and Gunawardena, J. (2016) Information integration and energy expenditure in gene regulation. Cell, 166, 234–244

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