1932

Abstract

Embryonic development is highly complex and dynamic, requiring the coordination of numerous molecular and cellular events at precise times and places. Advances in imaging technology have made it possible to follow developmental processes at cellular, tissue, and organ levels over time as they take place in the intact embryo. Parallel innovations of in vivo probes permit imaging to report on molecular, physiological, and anatomical events of embryogenesis, but the resulting multidimensional data sets pose significant challenges for extracting knowledge. In this review, we discuss recent and emerging advances in imaging technologies, in vivo labeling, and data processing that offer the greatest potential for jointly deciphering the intricate cellular dynamics and the underlying molecular mechanisms. Our discussion of the emerging area of “image-omics” highlights both the challenges of data analysis and the promise of more fully embracing computation and data science for rapidly advancing our understanding of biology.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-biodatasci-072018-021305
2019-07-20
2024-04-24
Loading full text...

Full text loading...

/deliver/fulltext/biodatasci/2/1/annurev-biodatasci-072018-021305.html?itemId=/content/journals/10.1146/annurev-biodatasci-072018-021305&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Acloque H, Adams MS, Fishwick K, Bronner-Fraser M, Nieto MA 2009. Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. J. Clin. Investig. 119:1438–49
    [Google Scholar]
  2. 2. 
    Cheung KJ, Ewald AJ. 2016. A collective route to metastasis: seeding by tumor cell clusters. Science 352:167–69
    [Google Scholar]
  3. 3. 
    Davidson EH. 2006. The Regulatory Genome: Gene Regulatory Networks in Development and Evolution New York: Academic
  4. 4. 
    Oates AC, Gorfinkiel N, Gonzalez-Gaitan M, Heisenberg CP 2009. Quantitative approaches in developmental biology. Nat. Rev. Genet. 10:517–30
    [Google Scholar]
  5. 5. 
    Mavrakis M, Pourquie O, Lecuit T 2010. Lighting up developmental mechanisms: how fluorescence imaging heralded a new era. Development 137:373–87
    [Google Scholar]
  6. 6. 
    Miyawaki A. 2011. Proteins on the move: insights gained from fluorescent protein technologies. Nat. Rev. Mol. Cell Biol. 12:656–68
    [Google Scholar]
  7. 7. 
    Cremer C, Cremer T. 1978. Considerations on a laser-scanning-microscope with high resolution and depth of field. Microsc. Acta 81:31–40
    [Google Scholar]
  8. 8. 
    Denk W, Strickler JH, Webb WW 1990. Two-photon laser scanning fluorescence microscopy. Science 248:73–76
    [Google Scholar]
  9. 9. 
    Potter SM, Wang CM, Garrity PA, Fraser SE 1996. Intravital imaging of green fluorescent protein using two-photon laser-scanning microscopy. Gene 173:25–31
    [Google Scholar]
  10. 10. 
    Dickinson ME, Bearman G, Tille S, Lansford R, Fraser SE 2001. Multi-spectral imaging and linear unmixing add a whole new dimension to laser scanning fluorescence microscopy. Biotechniques 31:1272–78
    [Google Scholar]
  11. 11. 
    Stringari C, Sierra R, Donovan PJ, Gratton E 2012. Label-free separation of human embryonic stem cells and their differentiating progenies by phasor fluorescence lifetime microscopy. J. Biomed. Opt. 17:046012
    [Google Scholar]
  12. 12. 
    Supatto W, Debarre D, Moulia B, Brouzes E, Martin JL et al. 2005. In vivo modulation of morphogenetic movements in Drosophila embryos with femtosecond laser pulses. PNAS 102:1047–52
    [Google Scholar]
  13. 13. 
    Supatto W, McMahon A, Fraser SE, Stathopoulos A 2009. Quantitative imaging of collective cell migration during Drosophila gastrulation: multiphoton microscopy and computational analysis. Nat. Protoc. 4:1397–412
    [Google Scholar]
  14. 14. 
    Rebollo E, Roldan M, Gonzalez C 2009. Spindle alignment is achieved without rotation after the first cell cycle in Drosophila embryonic neuroblasts. Development 136:3393–97
    [Google Scholar]
  15. 15. 
    McMahon A, Supatto W, Fraser SE, Stathopoulos A 2008. Dynamic analyses of Drosophila gastrulation provide insights into collective cell migration. Science 322:1546–50
    [Google Scholar]
  16. 16. 
    Olivier N, Luengo-Oroz MA, Duloquin L, Faure E, Savy T et al. 2010. Cell lineage reconstruction of early zebrafish embryos using label-free nonlinear microscopy. Science 329:967–71
    [Google Scholar]
  17. 17. 
    Sato Y, Poynter G, Huss D, Filla MB, Czirok A et al. 2010. Dynamic analysis of vascular morphogenesis using transgenic quail embryos. PLOS ONE 5:e12674
    [Google Scholar]
  18. 18. 
    Benazeraf B, Beaupeux M, Tchernookov M, Wallingford A, Salisbury T et al. 2017. Multi-scale quantification of tissue behavior during amniote embryo axis elongation. Development 144:4462–72
    [Google Scholar]
  19. 19. 
    Squirrell JM, Wokosin DL, White JG, Bavister BD 1999. Long-term two-photon fluorescence imaging of mammalian embryos without compromising viability. Nat. Biotechnol. 17:763–67
    [Google Scholar]
  20. 20. 
    McDole K, Xiong Y, Iglesias PA, Zheng Y 2011. Lineage mapping the pre-implantation mouse embryo by two-photon microscopy, new insights into the segregation of cell fates. Dev. Biol. 355:239–49
    [Google Scholar]
  21. 21. 
    Truong TV, Supatto W, Koos DS, Choi JM, Fraser SE 2011. Deep and fast live imaging with two-photon scanned light-sheet microscopy. Nat. Methods 8:757–60
    [Google Scholar]
  22. 22. 
    Debarre D, Olivier N, Supatto W, Beaurepaire E 2014. Mitigating phototoxicity during multiphoton microscopy of live Drosophila embryos in the 1.0–1.2 μm wavelength range. PLOS ONE 9:e104250
    [Google Scholar]
  23. 23. 
    Mohler W, Millard AC, Campagnola PJ 2003. Second harmonic generation imaging of endogenous structural proteins. Methods 29:97–109
    [Google Scholar]
  24. 24. 
    Kwan AC, Dombeck DA, Webb WW 2008. Polarized microtubule arrays in apical dendrites and axons. PNAS 105:11370–75
    [Google Scholar]
  25. 25. 
    Debarre D, Botcherby EJ, Watanabe T, Srinivas S, Booth MJ, Wilson T 2009. Image-based adaptive optics for two-photon microscopy. Opt. Lett. 34:2495–97
    [Google Scholar]
  26. 26. 
    Lin JH, Lai ND, Chiu CH, Lin CY, Rieger GW et al. 2008. Fabrication of spatial modulated second order nonlinear structures and quasi-phase matched second harmonic generation in a poled azo-copolymer planar waveguide. Opt. Express 16:7832–41
    [Google Scholar]
  27. 27. 
    Pantazis P, Maloney J, Wu D, Fraser SE 2010. Second harmonic generating (SHG) nanoprobes for in vivo imaging. PNAS 107:14535–40
    [Google Scholar]
  28. 28. 
    Tserevelakis GJ, Megalou EV, Filippidis G, Petanidou B, Fotakis C, Tavernarakis N 2014. Label-free imaging of lipid depositions in C. elegans using third-harmonic generation microscopy. PLOS ONE 9:e84431
    [Google Scholar]
  29. 29. 
    LeBert DC, Squirrell JM, Huttenlocher A, Eliceiri KW 2016. Second harmonic generation microscopy in zebrafish. Methods Cell Biol 133:55–68
    [Google Scholar]
  30. 30. 
    Barad Y, Eisenberg H, Horowitz M, Silberberg Y 1997. Nonlinear scanning laser microscopy by third harmonic generation. Appl. Phys. Lett. 70:922–24
    [Google Scholar]
  31. 31. 
    Oron D, Yelin D, Tal E, Raz S, Fachima R, Silberberg Y 2004. Depth-resolved structural imaging by third-harmonic generation microscopy. J. Struct. Biol. 147:3–11
    [Google Scholar]
  32. 32. 
    Jesacher A, Thayil A, Grieve K, Debarre D, Watanabe T et al. 2009. Adaptive harmonic generation microscopy of mammalian embryos. Opt. Lett. 34:3154–56
    [Google Scholar]
  33. 33. 
    Debarre D, Beaurepaire E. 2007. Quantitative characterization of biological liquids for third-harmonic generation microscopy. Biophys. J. 92:603–12
    [Google Scholar]
  34. 34. 
    Thayil A, Watanabe T, Jesacher A, Wilson T, Srinivas S, Booth M 2011. Long-term imaging of mouse embryos using adaptive harmonic generation microscopy. J. Biomed. Opt. 16:046018
    [Google Scholar]
  35. 35. 
    Chaigneau E, Wright AJ, Poland SP, Girkin JM, Silver RA 2011. Impact of wavefront distortion and scattering on 2-photon microscopy in mammalian brain tissue. Opt. Express 19:22755–74
    [Google Scholar]
  36. 36. 
    Tao X, Fernandez B, Azucena O, Fu M, Garcia D et al. 2011. Adaptive optics confocal microscopy using direct wavefront sensing. Opt. Lett. 36:1062–64
    [Google Scholar]
  37. 37. 
    Ji N, Sato TR, Betzig E 2012. Characterization and adaptive optical correction of aberrations during in vivo imaging in the mouse cortex. PNAS 109:22–27
    [Google Scholar]
  38. 38. 
    Olivier N, Mermillod-Blondin A, Arnold CB, Beaurepaire E 2009. Two-photon microscopy with simultaneous standard and extended depth of field using a tunable acoustic gradient-index lens. Opt. Lett. 34:1684–86
    [Google Scholar]
  39. 39. 
    Botcherby EJ, Juskaitis R, Wilson T 2006. Scanning two photon fluorescence microscopy with extended depth of field. Opt. Commun. 268:253–60
    [Google Scholar]
  40. 40. 
    Dufour P, Piché M, De Koninck Y, McCarthy N 2006. Two-photon excitation fluorescence microscopy with a high depth of field using an axicon. Appl. Opt. 45:9246–52
    [Google Scholar]
  41. 41. 
    Theriault G, De Koninck Y, McCarthy N 2013. Extended depth of field microscopy for rapid volumetric two-photon imaging. Opt. Express 21:10095–104
    [Google Scholar]
  42. 42. 
    Rodriguez C, Liang Y, Lu R, Ji N 2018. Three-photon fluorescence microscopy with an axially elongated Bessel focus. Opt. Lett. 43:1914–17
    [Google Scholar]
  43. 43. 
    Ji N. 2017. Adaptive optical fluorescence microscopy. Nat. Methods 14:374–80
    [Google Scholar]
  44. 44. 
    Lu R, Sun W, Liang Y, Kerlin A, Bierfeld J et al. 2017. Video-rate volumetric functional imaging of the brain at synaptic resolution. Nat. Neurosci. 20:620–28
    [Google Scholar]
  45. 45. 
    Song A, Charles AS, Koay SA, Gauthier JL, Thiberge SY et al. 2017. Volumetric two-photon imaging of neurons using stereoscopy (vTwINS). Nat. Methods 14:420–26
    [Google Scholar]
  46. 46. 
    Rodriguez P, Braun H, Kolodziej KE, de Boer E, Campbell J et al. 2006. Isolation of transcription factor complexes by in vivo biotinylation tagging and direct binding to streptavidin beads. Methods Mol. Biol. 338:305–23
    [Google Scholar]
  47. 47. 
    Weber M, Huisken J. 2011. Light sheet microscopy for real-time developmental biology. Curr. Opin. Genet. Dev. 21:566–72
    [Google Scholar]
  48. 48. 
    Hockendorf B, Thumberger T, Wittbrodt J 2012. Quantitative analysis of embryogenesis: a perspective for light sheet microscopy. Dev. Cell 23:1111–20
    [Google Scholar]
  49. 49. 
    de Medeiros G, Balazs B, Hufnagel L 2016. Light-sheet imaging of mammalian development. Semin. Cell Dev. Biol. 55:148–55
    [Google Scholar]
  50. 50. 
    Voie AH, Burns DH, Spelman FA 1993. Orthogonal-plane fluorescence optical sectioning: three-dimensional imaging of macroscopic biological specimens. J. Microsc. 170:229–36
    [Google Scholar]
  51. 51. 
    Huisken J, Swoger J, Del Bene F, Wittbrodt J, Stelzer EH 2004. Optical sectioning deep inside live embryos by selective plane illumination microscopy. Science 305:1007–9
    [Google Scholar]
  52. 52. 
    Keller PJ, Schmidt AD, Wittbrodt J, Stelzer EH 2008. Reconstruction of zebrafish early embryonic development by scanned light sheet microscopy. Science 322:1065–69
    [Google Scholar]
  53. 53. 
    Krzic U, Gunther S, Saunders TE, Streichan SJ, Hufnagel L 2012. Multiview light-sheet microscope for rapid in toto imaging. Nat. Methods 9:730–33
    [Google Scholar]
  54. 54. 
    Tomer R, Khairy K, Amat F, Keller PJ 2012. Quantitative high-speed imaging of entire developing embryos with simultaneous multiview light-sheet microscopy. Nat. Methods 9:755–63
    [Google Scholar]
  55. 55. 
    Royer LA, Lemon WC, Chhetri RK, Wan Y, Coleman M et al. 2016. Adaptive light-sheet microscopy for long-term, high-resolution imaging in living organisms. Nat. Biotechnol. 34:1267–78
    [Google Scholar]
  56. 56. 
    Udan RS, Piazza VG, Hsu CW, Hadjantonakis AK, Dickinson ME 2014. Quantitative imaging of cell dynamics in mouse embryos using light-sheet microscopy. Development 141:4406–14
    [Google Scholar]
  57. 57. 
    McDole K, Guignard L, Amat F, Berger A, Malandain G et al. 2018. In toto imaging and reconstruction of post-implantation mouse development at the single-cell level. Cell 175:859–76.e33
    [Google Scholar]
  58. 58. 
    Keller PJ, Stelzer EH. 2008. Quantitative in vivo imaging of entire embryos with digital scanned laser light sheet fluorescence microscopy. Curr. Opin. Neurobiol. 18:624–32
    [Google Scholar]
  59. 59. 
    Wu J, Li J, Chan RK 2013. A light sheet based high throughput 3D-imaging flow cytometer for phytoplankton analysis. Opt. Express 21:14474–80
    [Google Scholar]
  60. 60. 
    Chhetri RK, Amat F, Wan Y, Hockendorf B, Lemon WC, Keller PJ 2015. Whole-animal functional and developmental imaging with isotropic spatial resolution. Nat. Methods 12:1171–78
    [Google Scholar]
  61. 61. 
    Baumgart E, Kubitscheck U. 2012. Scanned light sheet microscopy with confocal slit detection. Opt. Express 20:21805–14
    [Google Scholar]
  62. 62. 
    Mei E, Fomitchov PA, Graves R, Campion M 2012. A line scanning confocal fluorescent microscope using a CMOS rolling shutter as an adjustable aperture. J. Microsc. 247:269–76
    [Google Scholar]
  63. 63. 
    Silvestri L, Bria A, Sacconi L, Iannello G, Pavone FS 2012. Confocal light sheet microscopy: micron-scale neuroanatomy of the entire mouse brain. Opt. Express 20:20582–98
    [Google Scholar]
  64. 64. 
    Fahrbach FO, Rohrbach A. 2012. Propagation stability of self-reconstructing Bessel beams enables contrast-enhanced imaging in thick media. Nat. Commun. 3:632
    [Google Scholar]
  65. 65. 
    de Medeiros G, Norlin N, Gunther S, Albert M, Panavaite L et al. 2015. Confocal multiview light-sheet microscopy. Nat. Commun. 6:8881
    [Google Scholar]
  66. 66. 
    Schmid B, Shah G, Scherf N, Weber M, Thierbach K et al. 2013. High-speed panoramic light-sheet microscopy reveals global endodermal cell dynamics. Nat. Commun. 4:2207
    [Google Scholar]
  67. 67. 
    Fu Q, Martin BL, Matus DQ, Gao L 2016. Imaging multicellular specimens with real-time optimized tiling light-sheet selective plane illumination microscopy. Nat. Commun. 7:11088
    [Google Scholar]
  68. 68. 
    Fahrbach FO, Voigt FF, Schmid B, Helmchen F, Huisken J 2013. Rapid 3D light-sheet microscopy with a tunable lens. Opt. Express 21:21010–26
    [Google Scholar]
  69. 69. 
    Planchon TA, Gao L, Milkie DE, Davidson MW, Galbraith JA et al. 2011. Rapid three-dimensional isotropic imaging of living cells using Bessel beam plane illumination. Nat. Methods 8:417–23
    [Google Scholar]
  70. 70. 
    Gao FS, Bai J, Zhang Q, Xu CB, Li Y 2012. Construction of multiple recombinant SLA-I proteins by linking heavy chains and light chains in vitro and analyzing their secondary and 3-dimensional structures. Gene 502:147–53
    [Google Scholar]
  71. 71. 
    Gao L, Zhu L, Li C, Wang LV 2014. Nonlinear light-sheet fluorescence microscopy by photobleaching imprinting. J. R. Soc. Interface 11:20130851
    [Google Scholar]
  72. 72. 
    Chen BC, Legant WR, Wang K, Shao L, Milkie DE et al. 2014. Lattice light-sheet microscopy: imaging molecules to embryos at high spatiotemporal resolution. Science 346:1257998
    [Google Scholar]
  73. 73. 
    Zhao M, Zhang H, Li Y, Ashok A, Liang R et al. 2014. Cellular imaging of deep organ using two-photon Bessel light-sheet nonlinear structured illumination microscopy. Biomed. Opt. Express 5:1296–308
    [Google Scholar]
  74. 74. 
    Zong W, Zhao J, Chen X, Lin Y, Ren H et al. 2015. Large-field high-resolution two-photon digital scanned light-sheet microscopy. Cell Res 25:254–57
    [Google Scholar]
  75. 75. 
    Liu TL, Upadhyayula S, Milkie DE, Singh V, Wang K et al. 2018. Observing the cell in its native state: imaging subcellular dynamics in multicellular organisms. Science 360:eaaq1392
    [Google Scholar]
  76. 76. 
    Palero J, Santos SI, Artigas D, Loza-Alvarez P 2010. A simple scanless two-photon fluorescence microscope using selective plane illumination. Opt. Express 18:8491–98
    [Google Scholar]
  77. 77. 
    Lavagnino Z, Zanacchi FC, Ronzitti E, Diaspro A 2013. Two-photon excitation selective plane illumination microscopy (2PE-SPIM) of highly scattering samples: characterization and application. Opt. Express 21:5998–6008
    [Google Scholar]
  78. 78. 
    Mahou P, Vermot J, Beaurepaire E, Supatto W 2014. Multicolor two-photon light-sheet microscopy. Nat. Methods 11:600–1
    [Google Scholar]
  79. 79. 
    Maruyama A, Oshima Y, Kajiura-Kobayashi H, Nonaka S, Imamura T, Naruse K 2014. Wide field intravital imaging by two-photon-excitation digital-scanned light-sheet microscopy (2p-DSLM) with a high-pulse energy laser. Biomed. Opt. Express 5:3311–25
    [Google Scholar]
  80. 80. 
    Lavagnino Z, Sancataldo G, d'Amora M, Follert P, De Pietri Tonelli D et al. 2016. 4D (x-y-z-t) imaging of thick biological samples by means of Two-Photon inverted Selective Plane Illumination Microscopy (2PE-iSPIM). Sci. Rep. 6:23923
    [Google Scholar]
  81. 81. 
    Levoy M, Ng R, Adams A, Footer M, Horowitz M 2006. Light field microscopy. ACM Trans. Graph. 25:924–34
    [Google Scholar]
  82. 82. 
    Nobauer T, Skocek O, Pernia-Andrade AJ, Weilguny L, Traub FM et al. 2017. Video rate volumetric Ca2+ imaging across cortex using seeded iterative demixing (SID) microscopy. Nat. Methods 14:811–18
    [Google Scholar]
  83. 83. 
    Wetts R, Fraser SE. 1991. Microinjection of fluorescent tracers to study neural cell lineages. Development 113(Suppl. 2):1–8:
    [Google Scholar]
  84. 84. 
    Mujumdar RB, Ernst LA, Mujumdar SR, Lewis CJ, Waggoner AS 1993. Cyanine dye labeling reagents: sulfoindocyanine succinimidyl esters. Bioconjug. Chem. 4:105–11
    [Google Scholar]
  85. 85. 
    Keppler A, Gendreizig S, Gronemeyer T, Pick H, Vogel H, Johnsson K 2003. A general method for the covalent labeling of fusion proteins with small molecules in vivo. Nat. Biotechnol. 21:86–89
    [Google Scholar]
  86. 86. 
    Gautier A, Juillerat A, Heinis C, Correa IR Jr., Kindermann M et al. 2008. An engineered protein tag for multiprotein labeling in living cells. Chem. Biol. 15:128–36
    [Google Scholar]
  87. 87. 
    Wu P, Shui W, Carlson BL, Hu N, Rabuka D et al. 2009. Site-specific chemical modification of recombinant proteins produced in mammalian cells by using the genetically encoded aldehyde tag. PNAS 106:3000–5
    [Google Scholar]
  88. 88. 
    Chalfie M, Tu Y, Euskirchen G, Ward WW, Prasher DC 1994. Green fluorescent protein as a marker for gene expression. Science 263:802–5
    [Google Scholar]
  89. 89. 
    Tsien RY. 1998. The green fluorescent protein. Annu. Rev. Biochem. 67:509–44
    [Google Scholar]
  90. 90. 
    Shaner NC, Lin MZ, McKeown MR, Steinbach PA, Hazelwood KL et al. 2008. Improving the photostability of bright monomeric orange and red fluorescent proteins. Nat. Methods 5:545–51
    [Google Scholar]
  91. 91. 
    Livet J, Weissman TA, Kang H, Draft RW, Lu J et al. 2007. Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system. Nature 450:56–62
    [Google Scholar]
  92. 92. 
    Germond A, Fujita H, Ichimura T, Watanabe TM 2016. Design and development of genetically encoded fluorescent sensors to monitor intracellular chemical and physical parameters. Biophys. Rev. 8:121–38
    [Google Scholar]
  93. 93. 
    Miyawaki A, Niino Y. 2015. Molecular spies for bioimaging—fluorescent protein-based probes. Mol. Cell 58:632–43
    [Google Scholar]
  94. 94. 
    Ormo M, Cubitt AB, Kallio K, Gross LA, Tsien RY, Remington SJ 1996. Crystal structure of the Aequorea victoria green fluorescent protein. Science 273:1392–95
    [Google Scholar]
  95. 95. 
    Labas YA, Gurskaya NG, Yanushevich YG, Fradkov AF, Lukyanov KA et al. 2002. Diversity and evolution of the green fluorescent protein family. PNAS 99:4256–61
    [Google Scholar]
  96. 96. 
    Zacharias DA, Violin JD, Newton AC, Tsien RY 2002. Partitioning of lipid-modified monomeric GFPs into membrane microdomains of live cells. Science 296:913–16
    [Google Scholar]
  97. 97. 
    Zhou S, Lo WC, Suhalim JL, Digman MA, Gratton E et al. 2012. Free extracellular diffusion creates the Dpp morphogen gradient of the Drosophila wing disc. Curr. Biol. 22:668–75
    [Google Scholar]
  98. 98. 
    Abu-Arish A, Porcher A, Czerwonka A, Dostatni N, Fradin C 2010. High mobility of bicoid captured by fluorescence correlation spectroscopy: implication for the rapid establishment of its gradient. Biophys. J. 99:L33–35
    [Google Scholar]
  99. 99. 
    Yu SR, Burkhardt M, Nowak M, Ries J, Petrasek Z et al. 2009. Fgf8 morphogen gradient forms by a source-sink mechanism with freely diffusing molecules. Nature 461:533–36
    [Google Scholar]
  100. 100. 
    Gregor T, Wieschaus EF, McGregor AP, Bialek W, Tank DW 2007. Stability and nuclear dynamics of the bicoid morphogen gradient. Cell 130:141–52
    [Google Scholar]
  101. 101. 
    Kicheva A, Pantazis P, Bollenbach T, Kalaidzidis Y, Bittig T et al. 2007. Kinetics of morphogen gradient formation. Science 315:521–25
    [Google Scholar]
  102. 102. 
    Schwank G, Dalessi S, Yang SF, Yagi R, de Lachapelle AM et al. 2011. Formation of the long range Dpp morphogen gradient. PLOS Biol 9:e1001111
    [Google Scholar]
  103. 103. 
    Heim R, Tsien RY. 1996. Engineering green fluorescent protein for improved brightness, longer wavelengths and fluorescence resonance energy transfer. Curr. Biol. 6:178–82
    [Google Scholar]
  104. 104. 
    Rodriguez EA, Tran GN, Gross LA, Crisp JL, Shu X et al. 2016. A far-red fluorescent protein evolved from a cyanobacterial phycobiliprotein. Nat. Methods 13:763–69
    [Google Scholar]
  105. 105. 
    Shaner NC, Campbell RE, Steinbach PA, Giepmans BN, Palmer AE, Tsien RY 2004. Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein. Nat. Biotechnol. 22:1567–72
    [Google Scholar]
  106. 106. 
    Bindels DS, Haarbosch L, van Weeren L, Postma M, Wiese KE et al. 2017. mScarlet: a bright monomeric red fluorescent protein for cellular imaging. Nat. Methods 14:53–56
    [Google Scholar]
  107. 107. 
    Rodriguez EA, Campbell RE, Lin JY, Lin MZ, Miyawaki A et al. 2017. The growing and glowing toolbox of fluorescent and photoactive proteins. Trends Biochem. Sci. 42:111–29
    [Google Scholar]
  108. 108. 
    Shaner NC, Steinbach PA, Tsien RY 2005. A guide to choosing fluorescent proteins. Nat. Methods 2:905–9
    [Google Scholar]
  109. 109. 
    Hadjieconomou D, Rotkopf S, Alexandre C, Bell DM, Dickson BJ, Salecker I 2011. Flybow: genetic multicolor cell labeling for neural circuit analysis in Drosophila melanogaster. Nat. Methods 8:260–66
    [Google Scholar]
  110. 110. 
    Kanca O, Caussinus E, Denes AS, Percival-Smith A, Affolter M 2014. Raeppli: a whole-tissue labeling tool for live imaging of Drosophila development. Development 141:472–80
    [Google Scholar]
  111. 111. 
    Gupta V, Poss KD. 2012. Clonally dominant cardiomyocytes direct heart morphogenesis. Nature 484:479–84
    [Google Scholar]
  112. 112. 
    Chen CH, Puliafito A, Cox BD, Primo L, Fang Y et al. 2016. Multicolor cell barcoding technology for long-term surveillance of epithelial regeneration in zebrafish. Dev. Cell 36:668–80
    [Google Scholar]
  113. 113. 
    Tabansky I, Lenarcic A, Draft RW, Loulier K, Keskin DB et al. 2013. Developmental bias in cleavage-stage mouse blastomeres. Curr. Biol. 23:21–31
    [Google Scholar]
  114. 114. 
    Pan YA, Freundlich T, Weissman TA, Schoppik D, Wang XC et al. 2013. Zebrabow: multispectral cell labeling for cell tracing and lineage analysis in zebrafish. Development 140:2835–46
    [Google Scholar]
  115. 115. 
    Cai D, Cohen KB, Luo T, Lichtman JW, Sanes JR 2013. Improved tools for the Brainbow toolbox. Nat. Methods 10:540–47
    [Google Scholar]
  116. 116. 
    Ritsma L, Ellenbroek SIJ, Zomer A, Snippert HJ, de Sauvage FJ et al. 2014. Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live imaging. Nature 507:362–65
    [Google Scholar]
  117. 117. 
    Nienhaus K, Nienhaus GU. 2014. Fluorescent proteins for live-cell imaging with super-resolution. Chem. Soc. Rev. 43:1088–106
    [Google Scholar]
  118. 118. 
    Adam V, Berardozzi R, Byrdin M, Bourgeois D 2014. Phototransformable fluorescent proteins: future challenges. Curr. Opin. Chem. Biol. 20:92–102
    [Google Scholar]
  119. 119. 
    Muller P, Rogers KW, Jordan BM, Lee JS, Robson D et al. 2012. Differential diffusivity of Nodal and Lefty underlies a reaction-diffusion patterning system. Science 336:721–24
    [Google Scholar]
  120. 120. 
    Plachta N, Bollenbach T, Pease S, Fraser SE, Pantazis P 2011. Oct4 kinetics predict cell lineage patterning in the early mammalian embryo. Nat. Cell Biol. 13:117–23
    [Google Scholar]
  121. 121. 
    Kaur G, Costa MW, Nefzger CM, Silva J, Fierro-Gonzalez JC et al. 2013. Probing transcription factor diffusion dynamics in the living mammalian embryo with photoactivatable fluorescence correlation spectroscopy. Nat. Commun. 4:1637
    [Google Scholar]
  122. 122. 
    Gurskaya NG, Verkhusha VV, Shcheglov AS, Staroverov DB, Chepurnykh TV et al. 2006. Engineering of a monomeric green-to-red photoactivatable fluorescent protein induced by blue light. Nat. Biotechnol. 24:461–65
    [Google Scholar]
  123. 123. 
    McKinney SA, Murphy CS, Hazelwood KL, Davidson MW, Looger LL 2009. A bright and photostable photoconvertible fluorescent protein. Nat. Methods 6:131–33
    [Google Scholar]
  124. 124. 
    Zhang M, Chang H, Zhang Y, Yu J, Wu L et al. 2012. Rational design of true monomeric and bright photoactivatable fluorescent proteins. Nat. Methods 9:727–29
    [Google Scholar]
  125. 125. 
    Subach OM, Entenberg D, Condeelis JS, Verkhusha VV 2012. A FRET-facilitated photoswitching using an orange fluorescent protein with the fast photoconversion kinetics. J. Am. Chem. Soc. 134:14789–99
    [Google Scholar]
  126. 126. 
    Dempsey WP, Georgieva L, Helbling PM, Sonay AY, Truong TV et al. 2015. In vivo single-cell labeling by confined primed conversion. Nat. Methods 12:645–48
    [Google Scholar]
  127. 127. 
    Mohr MA, Kobitski AY, Sabater LR, Nienhaus K, Obara CJ et al. 2017. Rational engineering of photoconvertible fluorescent proteins for dual-color fluorescence nanoscopy enabled by a triplet-state mechanism of primed conversion. Angew. Chem. 56:11628–33
    [Google Scholar]
  128. 128. 
    Tanner CC, Migdal CJ, Jones MT 1998. The Clipmap: a virtual mipmap. Proceedings of the 25th Annual Conference on Computer Graphics and Interactive Techniques151–58 New York: Assoc. Comput. Mach.
    [Google Scholar]
  129. 129. 
    Meagher D. 1980. High-speed image generation of complex solid objects using octree encoding European Patent EP0152741B
  130. 130. 
    Hadwiger M, Beyer J, Jeong WK, Pfister H 2012. Interactive volume exploration of petascale microscopy data streams using a visualization-driven virtual memory approach. IEEE Trans. Vis. Comput. Graphics 18:2285–92
    [Google Scholar]
  131. 131. 
    Fogal T, Schiewe A, Kruger J 2013. An analysis of scalable GPU-based ray-guided volume rendering. Proceedings of the IEEE Symposium on Large Data Analysis and Visualization 2013 B Geveci, H Pfister, V Vishwanath43–50 Los Alamitos, CA: IEEE Comput. Soc.
    [Google Scholar]
  132. 132. 
    Beyer J, Hadwiger M, Pfister H 2014. A survey of GPU-based large-scale volume visualization. Comput. Graphics Forum 34:813–37
    [Google Scholar]
  133. 133. 
    Laine S, Karras T. 2011. Efficient sparse voxel octrees. IEEE Trans. Vis. Comput. Graph. 17:1048–59
    [Google Scholar]
  134. 134. 
    Kraus M, Ertl T. 2002. Adaptive texture maps. Proceedings of the ACM SIGGRAPH/EUROGRAPHICS Conference on Graphics Hardware7–15 Aire-la-Ville, Switz.: Eurographics Assoc.
    [Google Scholar]
  135. 135. 
    Wan Y, Otsuna H, Chien CB, Hansen C 2009. An interactive visualization tool for multi-channel confocal microscopy data in neurobiology research. IEEE Trans. Vis. Comput. Graphics 15:1489–96
    [Google Scholar]
  136. 136. 
    Rueden C, Eliceiri KW, White JG 2004. VisBio: a computational tool for visualization of multidimensional biological image data. Traffic 5:411–17
    [Google Scholar]
  137. 137. 
    Joshi A, Scheinost D, Okuda H, Belhachemi D, Murphy I et al. 2011. Unified framework for development, deployment and robust testing of neuroimaging algorithms. Neuroinformatics 9:69–84
    [Google Scholar]
  138. 138. 
    Crassin C, Lefebvre S, Eisemann E 2009. GigaVoxels: ray-guided streaming for efficient and detailed voxel rendering. Proceedings of the 2009 Symposium on Interactive 3D Graphics and Games15–22 New York: Assoc. Comput. Mach.
    [Google Scholar]
  139. 139. 
    Kankaanpaa P, Paavolainen L, Tiitta S, Karjalainen M, Paivarinne J et al. 2012. BioImageXD: an open, general-purpose and high-throughput image-processing platform. Nat. Methods 9:683–89
    [Google Scholar]
  140. 140. 
    Peng H, Ruan Z, Long F, Simpson JH, Myers EW 2010. V3D enables real-time 3D visualization and quantitative analysis of large-scale biological image data sets. Nat. Biotechnol. 28:348–53
    [Google Scholar]
  141. 141. 
    Peng H, Bria A, Zhou Z, Iannello G, Long F 2014. Extensible visualization and analysis for multidimensional images using Vaa3D. Nat. Protoc. 9:193–208
    [Google Scholar]
  142. 142. 
    Wallis JW, Miller TR, Lerner CA, Kleerup EC 1989. Three-dimensional display in nuclear medicine. IEEE Trans. Med. Imaging 8:297–303
    [Google Scholar]
  143. 143. 
    Everitt C. 1999. Interactive order-independent transparency White Pap. Nvidia Corp. Santa Clara, CA:
  144. 144. 
    Kreeger K, Kaufman A. 1999. Mixing translucent polygons with volumes. Proceedings of Visualization '99 D Ebert, M Gross, B Hamann191–98 Los Alamitos, CA: IEEE Comput. Soc.
    [Google Scholar]
  145. 145. 
    Wallace CT, St. Croix CM, Watkins SC. 2015. Data management and archiving in a large microscopy-and-imaging, multi-user facility: problems and solutions. Mol. Reprod. Dev. 82:630–34
    [Google Scholar]
  146. 146. 
    Cunningham JP, Yu BM. 2014. Dimensionality reduction for large-scale neural recordings. Nat. Neurosci. 17:1500–9
    [Google Scholar]
  147. 147. 
    Dickinson ME, Flenniken AM, Ji X, Teboul L, Wong MD et al. 2016. High-throughput discovery of novel developmental phenotypes. Nature 537:508–14
    [Google Scholar]
  148. 148. 
    Preibisch S, Amat F, Stamataki E, Sarov M, Singer RH et al. 2014. Efficient Bayesian-based multiview deconvolution. Nat. Methods 11:645–48
    [Google Scholar]
  149. 149. 
    Amat F, Lemon W, Mossing DP, McDole K, Wan Y et al. 2014. Fast, accurate reconstruction of cell lineages from large-scale fluorescence microscopy data. Nat. Methods 11:951–58
    [Google Scholar]
  150. 150. 
    Digman MA, Caiolfa VR, Zamai M, Gratton E 2008. The phasor approach to fluorescence lifetime imaging analysis. Biophys. J. 94:L14–16
    [Google Scholar]
  151. 151. 
    Andrews LM, Jones MR, Digman MA, Gratton E 2013. Spectral phasor analysis of Pyronin Y labeled RNA microenvironments in living cells. Biomed. Opt. Express 4:171–77
    [Google Scholar]
  152. 152. 
    Fereidouni F, Bader AN, Gerritsen HC 2012. Spectral phasor analysis allows rapid and reliable unmixing of fluorescence microscopy spectral images. Biomed. Opt. Express 20:12729–41
    [Google Scholar]
  153. 153. 
    Sosnik J, Zheng L, Rackauckas CV, Digman M, Gratton E et al. 2016. Noise modulation in retinoic acid signaling sharpens segmental boundaries of gene expression in the embryonic zebrafish hindbrain. eLife 5:e14034
    [Google Scholar]
  154. 154. 
    Stringari C,Cinquin A, Cinquin O, Digman MA, Donovan PJ Gratton E 2011. Phasor approach to fluorescence lifetime microscopy distinguishes different metabolic states of germ cells in a live tissue. PNAS 108:13582–87
    [Google Scholar]
  155. 155. 
    Cutrale F, Salih A, Gratton E 2013. Spectral Phasor approach for fingerprinting of photo-activatable fluorescent proteins Dronpa, Kaede and KikGR. Methods Appl. Fluoresc. 1:35001
    [Google Scholar]
  156. 156. 
    Cutrale F, Trivedi V, Trinh LA, Chiu CL, Choi JM et al. 2017. Hyperspectral phasor analysis enables multiplexed 5D in vivo imaging. Nat. Methods 14:149–52
    [Google Scholar]
  157. 157. 
    Stringari C, Nourse JL, Flanagan LA, Gratton E 2012. Phasor fluorescence lifetime microscopy of free and protein-bound NADH reveals neural stem cell differentiation potential. PLOS ONE 7:e48014
    [Google Scholar]
  158. 158. 
    Lanzano L, Coto Hernandez I, Castello M, Gratton E, Diaspro A, Vicidomini G 2015. Encoding and decoding spatio-temporal information for super-resolution microscopy. Nat. Commun. 6:6701
    [Google Scholar]
  159. 159. 
    Ranjit S, Malacrida L, Jameson DM, Gratton E 2018. Fit-free analysis of fluorescence lifetime imaging data using the phasor approach. Nat. Protoc. 13:1979–2004
    [Google Scholar]
  160. 160. 
    Stringari C, Edwards RA, Pate KT, Waterman ML, Donovan PJ, Gratton E 2012. Metabolic trajectory of cellular differentiation in small intestine by Phasor Fluorescence Lifetime Microscopy of NADH. Sci. Rep. 2:568
    [Google Scholar]
  161. 161. 
    Wright BK, Andrews LM, Markham J, Jones MR, Stringari C et al. 2012. NADH distribution in live progenitor stem cells by phasor-fluorescence lifetime image microscopy. Biophys. J. 103:L7–9
    [Google Scholar]
  162. 162. 
    Browne AW, Arnesano C, Harutyunyan N, Khuu T, Martinez JC et al. 2017. Structural and functional characterization of human stem-cell-derived retinal organoids by live imaging. Investig. Ophthalmol. Vis. Sci. 58:3311–18
    [Google Scholar]
  163. 163. 
    Lerner B, Clocksin WF, Dhanjal S, Hulten MA, Bishop CM 2001. Automatic signal classification in fluorescence in situ hybridization images. Cytometry 43:87–93
    [Google Scholar]
  164. 164. 
    Chen X, Zhou X, Wong ST 2006. Automated segmentation, classification, and tracking of cancer cell nuclei in time-lapse microscopy. IEEE Trans. Biomed. Eng. 53:762–66
    [Google Scholar]
  165. 165. 
    Wahlby C, Sintorn IM, Erlandsson F, Borgefors G, Bengtsson E 2004. Combining intensity, edge and shape information for 2D and 3D segmentation of cell nuclei in tissue sections. J. Microsc. 215:67–76
    [Google Scholar]
  166. 166. 
    Turetken E, Wang X, Becker CJ, Haubold C, Fua P 2017. Network flow integer programming to track elliptical cells in time-lapse sequences. IEEE Trans. Med. Imaging 36:942–51
    [Google Scholar]
  167. 167. 
    Malpica N, de Solorzano CO, Vaquero JJ, Santos A, Vallcorba I et al. 1997. Applying watershed algorithms to the segmentation of clustered nuclei. Cytometry 28:289–97
    [Google Scholar]
  168. 168. 
    Ortiz de Solorzano C, Garcia Rodriguez E, Jones A, Pinkel D, Gray JW et al. 1999. Segmentation of confocal microscope images of cell nuclei in thick tissue sections. J. Microsc. 193:212–26
    [Google Scholar]
  169. 169. 
    Cliffe A, Doupe DP, Sung H, Lim IK, Ong KH et al. 2017. Quantitative 3D analysis of complex single border cell behaviors in coordinated collective cell migration. Nat. Commun. 8:14905
    [Google Scholar]
  170. 170. 
    Schiegg M, Hanslovsky P, Haubold C, Koethe U, Hufnagel L, Hamprecht FA 2015. Graphical model for joint segmentation and tracking of multiple dividing cells. Bioinformatics 31:948–56
    [Google Scholar]
  171. 171. 
    Dufour A, Thibeaux R, Labruyere E, Guillen N, Olivo-Marin JC 2011. 3-D active meshes: fast discrete deformable models for cell tracking in 3-D time-lapse microscopy. IEEE Trans. Image Process. 20:1925–37
    [Google Scholar]
  172. 172. 
    Fernandez R, Das P, Mirabet V, Moscardi E, Traas J et al. 2010. Imaging plant growth in 4D: robust tissue reconstruction and lineaging at cell resolution. Nat. Methods 7:547–53
    [Google Scholar]
  173. 173. 
    Mosaliganti KR, Noche RR, Xiong F, Swinburne IA, Megason SG 2012. ACME: automated cell morphology extractor for comprehensive reconstruction of cell membranes. PLOS Comput. Biol. 8:e1002780
    [Google Scholar]
  174. 174. 
    Stegmaier J, Amat F, Lemon WC, McDole K, Wan Y et al. 2016. Real-time three-dimensional cell segmentation in large-scale microscopy data of developing embryos. Dev. Cell 36:225–40
    [Google Scholar]
  175. 175. 
    Khan Z, Wang YC, Wieschaus EF, Kaschube M 2014. Quantitative 4D analyses of epithelial folding during Drosophila gastrulation. Development 141:2895–900
    [Google Scholar]
  176. 176. 
    Dufour A, Shinin V, Tajbakhsh S, Guillen-Aghion N, Olivo-Marin JC, Zimmer C 2005. Segmenting and tracking fluorescent cells in dynamic 3-D microscopy with coupled active surfaces. IEEE Trans. Image Process. 14:1396–410
    [Google Scholar]
  177. 177. 
    Bise R, Yin Z, Kanade T 2011. Reliable cell tracking by global data association. Proceedings of the 2011 IEEE International Symposium on Biomedical Imaging1004–10 New York: IEEE
    [Google Scholar]
  178. 178. 
    Ulman V, Maska M, Magnusson KEG, Ronneberger O, Haubold C et al. 2017. An objective comparison of cell-tracking algorithms. Nat. Methods 14:1141–52
    [Google Scholar]
  179. 179. 
    Radaelli F, D'Alfonso L, Collini M, Mingozzi F, Marongiu L et al. 2017. μMAPPS: a novel phasor approach to second harmonic analysis for in vitro-in vivo investigation of collagen microstructure. Sci. Rep. 7:17468 Erratum. 2018 Sci. Rep. 8:6314
    [Google Scholar]
  180. 180. 
    Ounkomol C, Seshamani S, Maleckar MM, Collman F, Johnson GR 2018. Label-free prediction of three-dimensional fluorescence images from transmitted-light microscopy. Nat. Methods 15:917–20
    [Google Scholar]
  181. 181. 
    Weigert M, Schmidt U, Boothe T, Muller A, Dibrov A et al. 2018. Content-aware image restoration: pushing the limits of fluorescence microscopy. Nat. Methods 15:1090–97
    [Google Scholar]
  182. 182. 
    Heylman C, Datta R, Sobrino A, George S, Gratton E 2015. Supervised machine learning for classification of the electrophysiological effects of chronotropic drugs on human induced pluripotent stem cell-derived cardiomyocytes. PLOS ONE 10:e0144572
    [Google Scholar]
  183. 183. 
    Buggenthin F, Buettner F, Hoppe PS, Endele M, Kroiss M et al. 2017. Prospective identification of hematopoietic lineage choice by deep learning. Nat. Methods 14:403–6
    [Google Scholar]
  184. 184. 
    Kraus OZ, Grys BT, Ba J, Chong Y, Frey BJ et al. 2017. Automated analysis of high-content microscopy data with deep learning. Mol. Syst. Biol. 13:924
    [Google Scholar]
  185. 185. 
    Christiansen EM, Yang SJ, Ando DM, Javaherian A, Skibinski G et al. 2018. In silico labeling: predicting fluorescent labels in unlabeled images. Cell 173:792–803.e19
    [Google Scholar]
  186. 186. 
    Ouyang W, Aristov A, Lelek M, Hao X, Zimmer C 2018. Deep learning massively accelerates super-resolution localization microscopy. Nat. Biotechnol. 36:460–68
    [Google Scholar]
  187. 187. 
    Chollet F. 2018. Deep Learning with Python Shelter Island, NY: Manning
  188. 188. 
    Piccinini F, Balassa T, Szkalisity A, Molnar C, Paavolainen L et al. 2017. Advanced cell classifier: user-friendly machine-learning-based software for discovering phenotypes in high-content imaging data. Cell Syst 4:651–55.e5
    [Google Scholar]
  189. 189. 
    Hughes AJ, Mornin JD, Biswas SK, Beck LE, Bauer DP et al. 2018. Quanti.us: a tool for rapid, flexible, crowd-based annotation of images. Nat. Methods 15:587–90
    [Google Scholar]
  190. 190. 
    Hardin J. 2002. Gastrulation: morphogenic movements Web Tutor. http://worms.zoology.wisc.edu/frogs/gast/gast_morph.html
  191. 191. 
    Shimomura O, Johnson F, Saida Y 1962. Extraction, purification and properties of aequorin, a bioluminescent protein from the luminous hydromedusan, Aequorea. J. Cell. Physiol. 59:223–39
    [Google Scholar]
  192. 192. 
    Wayland H, Hock J. 1974. Application of fluorescence vital microscopy to the vasculature around erupting teeth. Microsc. Res. 7:201–6
    [Google Scholar]
  193. 193. 
    Kino GS, Corle TR. 1989. Confocal scanning optical microscopy. Phys. Today 42:55–62
    [Google Scholar]
  194. 194. 
    Lichtman JW, Sunderland WJ, Wilkinson RS 1989. High-resolution imaging of synaptic structure with a simple confocal microscope. New Biol 1:75–82
    [Google Scholar]
  195. 195. 
    Wachter RM, Elsliger MA, Kallio K, Hanson GT, Remington SJ 1998. Structural basis of spectral shifts in the yellow-emission variants of green fluorescent protein. Structure 6:1267–77
    [Google Scholar]
  196. 196. 
    Matz MV, Fradkov AF, Labas YA, Savitsky AP, Zaraisky AG et al. 1999. Fluorescent proteins from nonbioluminescent Anthozoa species. Nat. Biotechnol. 17:969–73
    [Google Scholar]
  197. 197. 
    Griesbeck O, Baird GS, Campbell RE, Zacharias DA, Tsien RY 2001. Reducing the environmental sensitivity of yellow fluorescent protein: mechanism and applications. J. Biol. Chem. 276:29188–94
    [Google Scholar]
  198. 198. 
    Bevis BJ, Glick BS. 2002. Rapidly maturing variants of the Discosoma red fluorescent protein (DsRed). Nat. Biotechnol. 20:83–87
    [Google Scholar]
  199. 199. 
    Patterson GH, Lippincott-Schwartz J. 2002. A photoactivatable GFP for selective photolabeling of proteins and cells. Science 297:1873–77
    [Google Scholar]
  200. 200. 
    Campbell RE, Tour O, Palmer AE, Steinbach PA, Baird GS et al. 2002. A monomeric red fluorescent protein. PNAS 99:7877–82
    [Google Scholar]
  201. 201. 
    Ando R, Hama H, Yamamoto-Hino M, Mizuno H, Miyawaki A 2002. An optical marker based on the UV-induced green-to-red photoconversion of a fluorescent protein. PNAS 99:12651–56
    [Google Scholar]
  202. 202. 
    Nagai T, Ibata K, Park ES, Kubota M, Mikoshiba K, Miyawaki A 2002. A variant of yellow fluorescent protein with fast and efficient maturation for cell-biological applications. Nat. Biotechnol. 20:87–90
    [Google Scholar]
  203. 203. 
    Wiedenmann J, Ivanchenko S, Oswald F, Schmitt F, Rocker C et al. 2004. EosFP, a fluorescent marker protein with UV-inducible green-to-red fluorescence conversion. PNAS 101:15905–10
    [Google Scholar]
  204. 204. 
    Ando R, Mizuno H, Miyawaki A 2004. Regulated fast nucleocytoplasmic shuttling observed by reversible protein highlighting. Science 306:1370–73
    [Google Scholar]
  205. 205. 
    Chudakov DM, Verkhusha VV, Staroverov DB, Souslova EA, Lukyanov S, Lukyanov KA 2004. Photoswitchable cyan fluorescent protein for protein tracking. Nat. Biotechnol. 22:1435–39
    [Google Scholar]
  206. 206. 
    Rizzo MA, Springer GH, Granada B, Piston DW 2004. An improved cyan fluorescent protein variant useful for FRET. Nat. Biotechnol. 22:445–49
    [Google Scholar]
  207. 207. 
    Karasawa S, Araki T, Nagai T, Mizuno H, Miyawaki A 2004. Cyan-emitting and orange-emitting fluorescent proteins as a donor/acceptor pair for fluorescence resonance energy transfer. Biochem. J. 381:307–12
    [Google Scholar]
  208. 208. 
    Tsutsui H, Karasawa S, Shimizu H, Nukina N, Miyawaki A 2005. Semi-rational engineering of a coral fluorescent protein into an efficient highlighter. EMBO Rep 6:233–38
    [Google Scholar]
  209. 209. 
    Merzlyak EM, Goedhart J, Shcherbo D, Bulina ME, Shcheglov AS et al. 2007. Bright monomeric red fluorescent protein with an extended fluorescence lifetime. Nat. Methods 4:555–57
    [Google Scholar]
  210. 210. 
    Huisken J, Stainier DY. 2007. Even fluorescence excitation by multidirectional selective plane illumination microscopy (mSPIM). Opt. Lett. 32:2608–10
    [Google Scholar]
  211. 211. 
    Sakaue-Sawano A, Kurokawa H, Morimura T, Hanyu A, Hama H et al. 2008. Visualizing spatiotemporal dynamics of multicellular cell-cycle progression. Cell 132:487–98
    [Google Scholar]
  212. 212. 
    Subach OM, Gundorov IS, Yoshimura M, Subach FV, Zhang J et al. 2008. Conversion of red fluorescent protein into a bright blue probe. Chem. Biol. 15:1116–24
    [Google Scholar]
  213. 213. 
    Subach FV, Malashkevich VN, Zencheck WD, Xiao H, Filonov GS et al. 2009. Photoactivation mechanism of PAmCherry based on crystal structures of the protein in the dark and fluorescent states. PNAS 106:21097–102
    [Google Scholar]
  214. 214. 
    Keller PJ, Schmidt AD, Santella A, Khairy K, Bao Z et al. 2010. Fast, high-contrast imaging of animal development with scanned light sheet-based structured-illumination microscopy. Nat. Methods 7:637–42
    [Google Scholar]
  215. 215. 
    Filonov GS, Piatkevich KD, Ting LM, Zhang J, Kim K, Verkhusha VV 2011. Bright and stable near-infrared fluorescent protein for in vivo imaging. Nat. Biotechnol. 29:757–61
    [Google Scholar]
  216. 216. 
    Shcherbakova DM, Verkhusha VV. 2013. Near-infrared fluorescent proteins for multicolor in vivo imaging. Nat. Methods 10:751–54
    [Google Scholar]
  217. 217. 
    Shaner NC, Lambert GG, Chammas A, Ni Y, Cranfill PJ et al. 2013. A bright monomeric green fluorescent protein derived from Branchiostoma lanceolatum. Nat. Methods 10:407–9
    [Google Scholar]
  218. 218. 
    Gebhardt JC, Suter DM, Roy R, Zhao ZW, Chapman AR et al. 2013. Single-molecule imaging of transcription factor binding to DNA in live mammalian cells. Nat. Methods 10:421–26
    [Google Scholar]
  219. 219. 
    Tomer R, Ye L, Hsueh B, Deisseroth K 2014. Advanced CLARITY for rapid and high-resolution imaging of intact tissues. Nat. Protoc. 9:1682–97
    [Google Scholar]
  220. 220. 
    Jahr W, Schmid B, Schmied C, Fahrbach FO, Huisken J 2015. Hyperspectral light sheet microscopy. Nat. Commun. 6:7990
    [Google Scholar]
  221. 221. 
    Valm AM, Cohen S, Legant WR, Melunis J, Hershberg U et al. 2017. Applying systems-level spectral imaging and analysis to reveal the organelle interactome. Nature 546:162–67
    [Google Scholar]
  222. 222. 
    Dou J, Vorobieva AA, Sheffler W, Doyle LA, Park H et al. 2018. De novo design of a fluorescence-activating β-barrel. Nature 561:485–91
    [Google Scholar]
  223. 223. 
    Kvilekval K, Fedorov D, Obara B, Singh A, Manjunath BS 2010. Bisque: a platform for bioimage analysis and management. Bioinformatics 26:544–52
    [Google Scholar]
  224. 224. 
    Carpenter AE, Jones TR, Lamprecht MR, Clarke C, Kang IH et al. 2006. CellProfiler: image analysis software for identifying and quantifying cell phenotypes. Genome Biol 7:R100
    [Google Scholar]
  225. 225. 
    Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M et al. 2012. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9:676–82
    [Google Scholar]
  226. 226. 
    de Chaumont F, Dallongeville S, Chenouard N, Herve N, Pop S et al. 2012. Icy: an open bioimage informatics platform for extended reproducible research. Nat. Methods 9:690–96
    [Google Scholar]
  227. 227. 
    Sommer C, Straehle C, Köthe U, Hamprecht FA 2011. ilastik: interactive learning and segmentation toolkit. Proceedings of the 2011 IEEE International Symposium on Biomedical Imaging230–33 New York: IEEE
    [Google Scholar]
  228. 228. 
    Tomancak P, Beaton A, Weiszmann R, Kwan E, Shu S et al. 2002. Systematic determination of patterns of gene expression during Drosophila embryogenesis. Genome Biol 3:RESEARCH0088
    [Google Scholar]
  229. 229. 
    Orloff DN, Iwasa JH, Martone ME, Ellisman MH, Kane CM 2013. The cell: an image library-CCDB: a curated repository of microscopy data. Nucleic Acids Res 41:D1241–50
    [Google Scholar]
  230. 230. 
    Richardson L, Venkataraman S, Stevenson P, Yang Y, Burton N et al. 2010. EMAGE mouse embryo spatial gene expression database: 2010 update. Nucleic Acids Res 38:D703–9
    [Google Scholar]
  231. 231. 
    Williams E, Moore J, Li SW, Rustici G, Tarkowska A et al. 2017. The Image Data Resource: a bioimage data integration and publication platform. Nat. Methods 14:775–81
    [Google Scholar]
  232. 232. 
    Adebayo S, McLeod K, Tudose I, Osumi-Sutherland D, Burdett T et al. 2016. PhenoImageShare: an image annotation and query infrastructure. J. Biomed. Semantics 7:35
    [Google Scholar]
/content/journals/10.1146/annurev-biodatasci-072018-021305
Loading
/content/journals/10.1146/annurev-biodatasci-072018-021305
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error