Control of Tissue Development by Morphogens

Literature Cited

1. 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. 99:4L33–35
   [Google Scholar]
2. Adler M, Alon U. 2018. Fold-change detection in biological systems. Curr. Opin. Syst. Biol. 8:81–89
   [Google Scholar]
3. Aguilar-Hidalgo D, Werner S, Wartlick O, González-Gaitán M, Friedrich BM, Jülicher F. 2018. Critical point in self-organized tissue growth. Phys. Rev. Lett. 120:19198102
   [Google Scholar]
4. Aguirre-Tamaral A, Guerrero I. 2021. Improving the understanding of cytoneme-mediated morphogen gradients by in silico modeling. PLOS Comput. Biol. 17:8e1009245
   [Google Scholar]
5. Akiyama T, Kamimura K, Firkus C, Takeo S, Shimmi O, Nakato H. 2008. Dally regulates Dpp morphogen gradient formation by stabilizing Dpp on the cell surface. Dev. Biol. 313:1408–19
   [Google Scholar]
6. Alexandre C, Baena-Lopez A, Vincent J-P. 2014. Patterning and growth control by membrane-tethered Wingless. Nature 505:7482180–85
   [Google Scholar]
7. Allen BL, Tenzen T, McMahon AP. 2007. The Hedgehog-binding proteins Gas1 and Cdo cooperate to positively regulate Shh signaling during mouse development. Genes Dev. 21:101244–57
   [Google Scholar]
8. Almuedo-Castillo M, Bläßle A, Mörsdorf D, Marcon L, Soh GH et al. 2018. Scale-invariant patterning by size-dependent inhibition of Nodal signalling. Nat. Cell Biol. 20:91032–42
   [Google Scholar]
9. Alon U. 2007. Network motifs: theory and experimental approaches. Nat. Rev. Genet. 8:6450–61
   [Google Scholar]
10. Athilingam T, Nelanuthala AVS, Breen C, Wohland T, Saunders TE. 2022. Long-ranged formation of the Bicoid gradient requires multiple dynamic modes that spatially vary across the embryo. bioRxiv 2022.09.28.509874. https://doi.org/10.1101/2022.09.28
11. Averbukh I, Ben-Zvi D, Mishra S, Barkai N. 2014. Scaling morphogen gradients during tissue growth by a cell division rule. Development 141:102150–56
    [Google Scholar]
12. Balaskas N, Ribeiro A, Panovska J, Dessaud E, Sasai N et al. 2012. Gene regulatory logic for reading the Sonic Hedgehog signaling gradient in the vertebrate neural tube. Cell 148:1–2273–84
    [Google Scholar]
13. Barolo S, Posakony JW. 2002. Three habits of highly effective signaling pathways: principles of transcriptional control by developmental cell signaling. Genes Dev. 16:101167–81
    [Google Scholar]
14. Barrio L, Milán M. 2020. Regulation of anisotropic tissue growth by two orthogonal signaling centers. Dev. Cell 52:659–72.e3
    [Google Scholar]
15. Barth KA, Kishimoto Y, Rohr KB, Seydler C, Schulte-Merker S, Wilson SW. 1999. Bmp activity establishes a gradient of positional information throughout the entire neural plate. Development 126:224977–87
    [Google Scholar]
16. Bénazéraf B, Francois P, Baker RE, Denans N, Little CD, Pourquié O. 2010. A random cell motility gradient downstream of FGF controls elongation of an amniote embryo. Nature 466:7303248–52
    [Google Scholar]
17. Ben-Zvi D, Barkai N. 2010. Scaling of morphogen gradients by an expansion-repression integral feedback control. PNAS 107:156924–29
    [Google Scholar]
18. Ben-Zvi D, Pyrowolakis G, Barkai N, Shilo B-Z. 2011. Expansion-repression mechanism for scaling the Dpp activation gradient in Drosophila wing imaginal discs. Curr. Biol. 21:161391–96
    [Google Scholar]
19. Ben-Zvi D, Shilo B-Z, Fainsod A, Barkai N. 2008. Scaling of the BMP activation gradient in Xenopus embryos. Nature 453:1205–11
    [Google Scholar]
20. Berezhkovskii AM, Sample C, Shvartsman SY. 2010. How long does it take to establish a morphogen gradient?. Biophysical J. 99:8L59–61
    [Google Scholar]
21. Bergmann S, Sandler O, Sberro H, Shnider S, Schejter E et al. 2007. Pre-steady-state decoding of the Bicoid morphogen gradient. PLOS Biol. 5:2e46
    [Google Scholar]
22. Bergsland M, Ramsköld D, Zaouter C, Klum S, Sandberg R, Muhr J. 2011. Sequentially acting Sox transcription factors in neural lineage development. Genes Dev. 25:232453–64
    [Google Scholar]
23. Bernheim S, Meilhac SM. 2020. Mesoderm patterning by a dynamic gradient of retinoic acid signalling. Philos. Trans. R. Soc. B Biol. Sci. 375:180920190556
    [Google Scholar]
24. Bischoff M, Gradilla A-C, Seijo I, Andrés G, Rodríguez-Navas C et al. 2013. Cytonemes are required for the establishment of a normal Hedgehog morphogen gradient in Drosophila epithelia. Nat. Cell Biol. 15:111269–81
    [Google Scholar]
25. Bittig T, Wartlick O, González-Gaitán M, Jülicher F. 2009. Quantification of growth asymmetries in developing epithelia. Eur. Phys. J. E 30:193–99
    [Google Scholar]
26. Blilou I, Xu J, Wildwater M, Willemsen V, Paponov I et al. 2005. The PIN auxin efflux facilitator network controls growth and patterning in Arabidopsis roots. Nature 433:702139–44
    [Google Scholar]
27. Bökel C, Schwabedissen A, Entchev E, Renaud O, González-Gaitán M. 2006. Sara endosomes and the maintenance of Dpp signaling levels across mitosis. Science 314:58021135–39
    [Google Scholar]
28. Bollenbach T, Kruse K, Pantazis P, González-Gaitán M, Jülicher F. 2005. Robust formation of morphogen gradients. Phys. Rev. Lett. 94:1018103
    [Google Scholar]
29. Bollenbach T, Kruse K, Pantazis P, González-Gaitán M, Jülicher F. 2007. Morphogen transport in epithelia. Phys. Rev. E 75:1011901
    [Google Scholar]
30. Bollenbach T, Pantazis P, Kicheva A, Bökel C, González-Gaitán M, Jülicher F. 2008. Precision of the Dpp gradient. Development 135:61137–46
    [Google Scholar]
31. Bornemann DJ, Duncan JE, Staatz W, Selleck S, Warrior R. 2004. Abrogation of heparan sulfate synthesis in Drosophila disrupts the Wingless, Hedgehog and Decapentaplegic signaling pathways. Development 131:91927–38
    [Google Scholar]
32. Bosch PS, Ziukaite R, Alexandre C, Basler K, Vincent J-P. 2017. Dpp controls growth and patterning in Drosophila wing precursors through distinct modes of action. eLife 6:e22546
    [Google Scholar]
33. Briscoe J, Chen Y, Jessell TM, Struhl G. 2001. A Hedgehog-insensitive form of patched provides evidence for direct long-range morphogen activity of Sonic Hedgehog in the neural tube. Mol. Cell 7:61279–91
    [Google Scholar]
34. Briscoe J, Pierani A, Jessell TM, Ericson J. 2000. A homeodomain protein code specifies progenitor cell identity and neuronal fate in the ventral neural tube. Cell 101:4435–45
    [Google Scholar]
35. Briscoe J, Small S. 2015. Morphogen rules: design principles of gradient-mediated embryo patterning. Development 142:233996–4009
    [Google Scholar]
36. Brunt L, Greicius G, Rogers S, Evans BD, Virshup DM et al. 2021. Vangl2 promotes the formation of long cytonemes to enable distant Wnt/β-catenin signaling. Nat. Commun. 12:12058
    [Google Scholar]
37. Burke R, Nellen D, Bellotto M, Hafen E, Senti KA et al. 1999. Dispatched, a novel sterol-sensing domain protein dedicated to the release of cholesterol-modified Hedgehog from signaling cells. Cell 99:7803–15
    [Google Scholar]
38. Cadigan KM, Fish MP, Rulifson EJ, Nusse R. 1998. Wingless repression of Drosophila frizzled 2 expression shapes the Wingless morphogen gradient in the wing. Cell 93:5767–77
    [Google Scholar]
39. Camacho-Aguilar E, Yoon S, Ortiz-Salazar MA, Warmflash A. 2022. Combinatorial interpretation of BMP and WNT allows BMP to act as a morphogen in time but not in concentration. bioRxiv 2022.11.11.516212. https://doi.org/10.1101/2022.11.11.516212
40. Cannavò E, Khoueiry P, Garfield DA, Geeleher P, Zichner T et al. 2016. Shadow enhancers are pervasive features of developmental regulatory networks. Curr. Biol. 26:138–51
    [Google Scholar]
41. Čapek D, Müller P. 2019. Positional information and tissue scaling during development and regeneration. Development 146:24dev177709
    [Google Scholar]
42. Cardin AD, Weintraub HJ. 1989. Molecular modeling of protein-glycosaminoglycan interactions. Arteriosclerosis 9:121–32
    [Google Scholar]
43. Caspary T, García-García MJ, Huangfu D, Eggenschwiler JT, Wyler MR et al. 2002. Mouse dispatched homolog1 is required for long-range, but not juxtacrine, Hh signaling. Curr. Biol. 12:181628–32
    [Google Scholar]
44. Chang Y-H, Sun YH. 2014. Carrier of Wingless (Cow), a secreted heparan sulfate proteoglycan, promotes extracellular transport of Wingless. PLOS ONE 9:10e111573
    [Google Scholar]
45. Chen H, Xu Z, Mei C, Yu D, Small S. 2012. A system of repressor gradients spatially organizes the boundaries of Bicoid-dependent target genes. Cell 149:3618–29
    [Google Scholar]
46. Chen M-H, Li Y-J, Kawakami T, Xu S-M, Chuang P-T. 2004. Palmitoylation is required for the production of a soluble multimeric Hedgehog protein complex and long-range signaling in vertebrates. Genes Dev. 18:6641–59
    [Google Scholar]
47. Cheung D, Miles C, Kreitman M, Ma J. 2011. Scaling of the Bicoid morphogen gradient by a volume-dependent production rate. Development 138:132741–49
    [Google Scholar]
48. Chiang C, Litingtung Y, Lee E, Young KE, Corden JL et al. 1996. Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 383:6599407–13
    [Google Scholar]
49. Clyde DE, Corado MSG, Wu X, Paré A, Papatsenko D, Small S. 2003. A self-organizing system of repressor gradients establishes segmental complexity in Drosophila. Nature 426:6968849–53
    [Google Scholar]
50. Cohen M, Page KM, Perez-Carrasco R, Barnes CP, Briscoe J. 2014. A theoretical framework for the regulation of Shh morphogen-controlled gene expression. Development 141:203868–78
    [Google Scholar]
51. Cohen-Saidon C, Cohen AA, Sigal A, Liron Y, Alon U. 2009. Dynamics and variability of ERK2 response to EGF in individual living cells. Mol. Cell 36:5885–93
    [Google Scholar]
52. Collins ZM, Ishimatsu K, Tsai TYC, Megason SG. 2018. A Scube2-Shh feedback loop links morphogen release to morphogen signaling to enable scale invariant patterning of the ventral neural tube. bioRxiv 469239. https://doi.org/10.1101/469239
53. Cotterell J, Sharpe J. 2010. An atlas of gene regulatory networks reveals multiple three-gene mechanisms for interpreting morphogen gradients. Mol. Syst. Biol. 6:425
    [Google Scholar]
54. Dalessi S, Neves A, Bergmann S. 2012. Modeling morphogen gradient formation from arbitrary realistically shaped sources. J. Theor. Biol. 294:130–38
    [Google Scholar]
55. Das D, Jülich D, Schwendinger-Schreck J, Guillon E, Lawton AK et al. 2019. Organization of embryonic morphogenesis via mechanical information. Dev. Cell 49:6829–39.e5
    [Google Scholar]
56. Davidson EH. 2010. Emerging properties of animal gene regulatory networks. Nature 468:7326911–20
    [Google Scholar]
57. Dessaud E, Ribes V, Balaskas N, Yang LL, Pierani A et al. 2010. Dynamic assignment and maintenance of positional identity in the ventral neural tube by the morphogen Sonic hedgehog. PLOS Biol. 8:6e1000382
    [Google Scholar]
58. Dessaud E, Yang LL, Hill K, Cox B, Ulloa F et al. 2007. Interpretation of the sonic hedgehog morphogen gradient by a temporal adaptation mechanism. Nature 450:7170717–20
    [Google Scholar]
59. Dickmann JEM, Rink JC, Jülicher F. 2022. Long-range morphogen gradient formation by cell-to-cell signal propagation. Phys. Biol. 19:6066001
    [Google Scholar]
60. Driever W, Nüsslein-Volhard C. 1988. The bicoid protein determines position in the Drosophila embryo in a concentration-dependent manner. Cell 54:195–104
    [Google Scholar]
61. Driever W, Thoma G, Nüsslein-Volhard C. 1989. Determination of spatial domains of zygotic gene expression in the Drosophila embryo by the affinity of binding sites for the bicoid morphogen. Nature 340:6232363–67
    [Google Scholar]
62. Drocco JA, Grimm O, Tank DW, Wieschaus E. 2011. Measurement and perturbation of morphogen lifetime: effects on gradient shape. Biophys. J. 101:81807–15
    [Google Scholar]
63. Du L, Sohr A, Yan G, Roy S. 2018. Feedback regulation of cytoneme-mediated transport shapes a tissue-specific FGF morphogen gradient. eLife 7:e38137
    [Google Scholar]
64. Dubrulle J, Jordan BM, Akhmetova L, Farrell JA, Kim S-H et al. 2015. Response to Nodal morphogen gradient is determined by the kinetics of target gene induction. eLife 4:e05042
    [Google Scholar]
65. Dubrulle J, Pourquié O. 2004. fgf8 mRNA decay establishes a gradient that couples axial elongation to patterning in the vertebrate embryo. Nature 427:6973419–22
    [Google Scholar]
66. Durrieu L, Kirrmaier D, Schneidt T, Kats I, Raghavan S et al. 2018. Bicoid gradient formation mechanism and dynamics revealed by protein lifetime analysis. Mol. Syst. Biol. 14:9e8355
    [Google Scholar]
67. Echelard Y, Epstein DJ, St-Jacques B, Shen L, Mohler J et al. 1993. Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell 75:71417–30
    [Google Scholar]
68. Eldar A, Dorfman R, Weiss D, Ashe H, Shilo B-Z, Barkai N. 2002. Robustness of the BMP morphogen gradient in Drosophila embryonic patterning. Nature 419:6904304–8
    [Google Scholar]
69. Eldar A, Rosin D, Shilo B-Z, Barkai N. 2003. Self-enhanced ligand degradation underlies robustness of morphogen gradients. Dev. Cell 5:4635–46
    [Google Scholar]
70. Ericson J, Rashbass P, Schedl A, Brenner-Morton S, Kawakami A et al. 1997. Pax6 controls progenitor cell identity and neuronal fate in response to graded Shh signaling. Cell 90:1169–80
    [Google Scholar]
71. Exelby K, Herrera-Delgado E, Perez LG, Perez-Carrasco R, Sagner A et al. 2021. Precision of tissue patterning is controlled by dynamical properties of gene regulatory networks. Development 148:4dev197566
    [Google Scholar]
72. Fernandes G, Tran H, Andrieu M, Diaw Y, Perez Romero C et al. 2022. Synthetic reconstruction of the hunchback promoter specifies the role of Bicoid, Zelda and Hunchback in the dynamics of its transcription. eLife 11:e74509
    [Google Scholar]
73. Foo SM, Sun Y, Lim B, Ziukaite R, O'Brien K et al. 2014. Zelda potentiates morphogen activity by increasing chromatin accessibility. Curr. Biol. 24:121341–46
    [Google Scholar]
74. Fried P, Iber D. 2014. Dynamic scaling of morphogen gradients on growing domains. Nat. Commun. 5:15077
    [Google Scholar]
75. Fujise M, Takeo S, Kamimura K, Matsuo T, Aigaki T et al. 2003. Dally regulates Dpp morphogen gradient formation in the Drosophila wing. Development 130:81515–22
    [Google Scholar]
76. Fulton T, Spiess K, Thomson L, Wang Y, Clark B et al. 2021. Cell rearrangement generates pattern emergence as a function of temporal morphogen exposure. bioRxiv 2021.02.05.429898. https://doi.org/10.1101/2021.02.05.429898
77. Fulton T, Verd B, Steventon B. 2022. The unappreciated generative role of cell movements in pattern formation. R. Soc. Open Sci. 9:4211293
    [Google Scholar]
78. Galinha C, Hofhuis H, Luijten M, Willemsen V, Blilou I et al. 2007. PLETHORA proteins as dose-dependent master regulators of Arabidopsis root development. Nature 449:71651053–57
    [Google Scholar]
79. Goentoro L, Kirschner MW. 2009. Evidence that fold-change, and not absolute level, of β-catenin dictates Wnt signaling. Mol. Cell 36:5872–84
    [Google Scholar]
80. Gorfinkiel N, Sierra J, Callejo A, Ibañez C, Guerrero I. 2005. The Drosophila ortholog of the human Wnt inhibitor factor Shifted controls the diffusion of lipid-modified Hedgehog. Dev. Cell 8:2241–53
    [Google Scholar]
81. Green JBA, Sharpe J. 2015. Positional information and reaction-diffusion: Two big ideas in developmental biology combine. Development 142:71203–11
    [Google Scholar]
82. Greenfeld H, Lin J, Mullins MC. 2021. The BMP signaling gradient is interpreted through concentration thresholds in dorsal-ventral axial patterning. PLOS Biol. 19:1e3001059
    [Google Scholar]
83. Gregor T, Bialek W, de Ruyter van Steveninck RR, Tank DW, Wieschaus EF. 2005. Diffusion and scaling during early embryonic pattern formation. PNAS 102:5118403–7
    [Google Scholar]
84. Gregor T, Tank DW, Wieschaus EF, Bialek W. 2007a. Probing the limits to positional information. Cell 130:1153–64
    [Google Scholar]
85. Gregor T, Wieschaus EF, McGregor AP, Bialek W, Tank DW. 2007b. Stability and nuclear dynamics of the Bicoid morphogen gradient. Cell 130:1141–52
    [Google Scholar]
86. Grieneisen VA, Xu J, Marée AFM, Hogeweg P, Scheres B. 2007. Auxin transport is sufficient to generate a maximum and gradient guiding root growth. Nature 449:71651008–13
    [Google Scholar]
87. Gritsman K, Talbot WS, Schier AF. 2000. Nodal signaling patterns the organizer. Development 127:921–32
    [Google Scholar]
88. Gross JC, Chaudhary V, Bartscherer K, Boutros M. 2012. Active Wnt proteins are secreted on exosomes. Nat. Cell Biol. 14:101036–45
    [Google Scholar]
89. Häcker U, Lin X, Perrimon N. 1997. The Drosophila sugarless gene modulates Wingless signaling and encodes an enzyme involved in polysaccharide biosynthesis. Development 124:183565–73
    [Google Scholar]
90. Haerry TE, Heslip TR, Marsh JL, O'Connor MB 1997. Defects in glucuronate biosynthesis disrupt Wingless signaling in Drosophila. Development 124:163055–64
    [Google Scholar]
91. Hagos EG, Dougan ST. 2007. Time-dependent patterning of the mesoderm and endoderm by Nodal signals in zebrafish. BMC Dev. Biol. 7:22
    [Google Scholar]
92. Hamaratoglu F, de Lachapelle AM, Pyrowolakis G, Bergmann S, Affolter M. 2011. Dpp signaling activity requires Pentagone to scale with tissue size in the growing Drosophila wing imaginal disc. PLOS Biol. 9:10e1001182
    [Google Scholar]
93. Harish RK, Gupta M, Zöller D, Hartmann H, Gheisari A et al. 2022. Real-time monitoring of endogenous Fgf8a gradient attests to its role as a morphogen during zebrafish gastrulation. bioRxiv 2022.04.26.488902. https://doi.org/10.1101/2022.04.26.488902
94. Harrison MM, Li X-Y, Kaplan T, Botchan MR, Eisen MB. 2011. Zelda binding in the early Drosophila melanogaster embryo marks regions subsequently activated at the maternal-to-zygotic transition. PLOS Genet. 7:10e1002266
    [Google Scholar]
95. Hollway GE, Maule J, Gautier P, Evans TM, Keenan DG et al. 2006. Scube2 mediates Hedgehog signalling in the zebrafish embryo. Dev. Biol. 294:1104–18
    [Google Scholar]
96. Hsieh JC, Kodjabachian L, Rebbert ML, Rattner A, Smallwood PM et al. 1999. A new secreted protein that binds to Wnt proteins and inhibits their activities. Nature 398:6726431–36
    [Google Scholar]
97. Hu Q, Ueno N, Behringer RR. 2004. Restriction of BMP4 activity domains in the developing neural tube of the mouse embryo. EMBO Rep. 5:7734–39
    [Google Scholar]
98. Huang A, Amourda C, Zhang S, Tolwinski NS, Saunders TE. 2017. Decoding temporal interpretation of the morphogen Bicoid in the early Drosophila embryo. eLife 6:e26258
    [Google Scholar]
99. Huang CY, Ferrell JE. 1996. Ultrasensitivity in the mitogen-activated protein kinase cascade. PNAS 93:1910078–83
    [Google Scholar]
100. Jaeger J. 2011. The gap gene network. Cell. Mol. Life Sci. 68:2243–74
     [Google Scholar]
101. Jaeger J, Surkova S, Blagov M, Janssens H, Kosman D et al. 2004. Dynamic control of positional information in the early Drosophila embryo. Nature 430:6997368–71
     [Google Scholar]
102. Jeong J, McMahon AP. 2005. Growth and pattern of the mammalian neural tube are governed by partially overlapping feedback activities of the hedgehog antagonists patched 1 and Hhip1. Development 132:1143–54
     [Google Scholar]
103. Jiang J, Levine M. 1993. Binding affinities and cooperative interactions with bHLH activators delimit threshold responses to the dorsal gradient morphogen. Cell 72:5741–52
     [Google Scholar]
104. Jullien J, Gurdon J. 2005. Morphogen gradient interpretation by a regulated trafficking step during ligand-receptor transduction. Genes Dev. 19:222682–94
     [Google Scholar]
105. Kanodia JS, Liang H-L, Kim Y, Lim B, Zhan M et al. 2012. Pattern formation by graded and uniform signals in the early Drosophila embryo. Biophys. J. 102:3427–33
     [Google Scholar]
106. Kawakami A, Nojima Y, Toyoda A, Takahoko M, Satoh M et al. 2005. The zebrafish-secreted matrix protein you/scube2 is implicated in long-range regulation of hedgehog signaling. Curr. Biol. 15:5480–88
     [Google Scholar]
107. Kawakami T, Kawcak T, Li Y-J, Zhang W, Hu Y, Chuang P-T. 2002. Mouse dispatched mutants fail to distribute hedgehog proteins and are defective in hedgehog signaling. Development 129:245753–65
     [Google Scholar]
108. Kicheva A, Bollenbach T, Ribeiro A, Valle HP, Lovell-Badge R et al. 2014. Coordination of progenitor specification and growth in mouse and chick spinal cord. Science 345:62041254927
     [Google Scholar]
109. Kicheva A, Bollenbach T, Wartlick O, Jülicher F, Gonzalez-Gaitan M. 2012. Investigating the principles of morphogen gradient formation: from tissues to cells. Curr. Opin. Genet. Dev. 22:6527–32
     [Google Scholar]
110. Kicheva A, Pantazis P, Bollenbach T, Kalaidzidis Y, Bittig T et al. 2007. Kinetics of morphogen gradient formation. Science 315:5811521–25
     [Google Scholar]
111. Klein T, Arias AM. 1998. Different spatial and temporal interactions between Notch, wingless, and vestigial specify proximal and distal pattern elements of the wing in Drosophila. Dev. Biol. 194:2196–212
     [Google Scholar]
112. Korkut C, Ataman B, Ramachandran P, Ashley J, Barria R et al. 2009. Trans-synaptic transmission of vesicular Wnt signals through Evi/Wntless. Cell 139:2393–404
     [Google Scholar]
113. Kornberg TB. 2017. Distributing signaling proteins in space and time: the province of cytonemes. Curr. Opin. Genet. Dev. 45:22–27
     [Google Scholar]
114. Kraut R, Levine M. 1991. Mutually repressive interactions between the gap genes giant and Krüppel define middle body regions of the Drosophila embryo. Development 111:2611–21
     [Google Scholar]
115. Kuhn T, Landge AN, Mörsdorf D, Coßmann J, Gerstenecker J et al. 2022. Single-molecule tracking of Nodal and Lefty in live zebrafish embryos supports hindered diffusion model. Nat. Commun. 13:16101
     [Google Scholar]
116. Lander AD, Lo W-C, Nie Q, Wan FYM. 2009. The measure of success: constraints, objectives, and tradeoffs in morphogen-mediated patterning. Cold Spring Harb. Perspect. Biol. 1:1a002022
     [Google Scholar]
117. Lecuit T, Cohen SM. 1998. Dpp receptor levels contribute to shaping the Dpp morphogen gradient in the Drosophila wing imaginal disc. Development 125:244901–7
     [Google Scholar]
118. Leyns L, Bouwmeester T, Kim SH, Piccolo S, De Robertis EM. 1997. Frzb-1 is a secreted antagonist of Wnt signaling expressed in the Spemann organizer. Cell 88:6747–56
     [Google Scholar]
119. Li L, Wang X, Chai J, Wang X, Buganza-Tepole A, Umulis DM. 2022. Determining the role of advection in patterning by bone morphogenetic proteins through neural network model-based acceleration of a 3D finite element model of the zebrafish embryo. Front. Syst. Biol. 2:983372
     [Google Scholar]
120. Li P, Markson JS, Wang S, Chen S, Vachharajani V, Elowitz MB. 2018. Morphogen gradient reconstitution reveals Hedgehog pathway design principles. Science 360:6388543–48
     [Google Scholar]
121. Li X-Y, Eisen MB. 2018. Zelda potentiates transcription factor binding to zygotic enhancers by increasing local chromatin accessibility during early Drosophila melanogaster embryogenesis. bioRxiv 380857. https://doi.org/10.1101/380857
122. Liégeois S, Benedetto A, Garnier J-M, Schwab Y, Labouesse M. 2006. The V0-ATPase mediates apical secretion of exosomes containing Hedgehog-related proteins in Caenorhabditis elegans. J. Cell Biol. 173:6949–61
     [Google Scholar]
123. Little SC, Tkačik G, Kneeland TB, Wieschaus EF, Gregor T. 2011. The formation of the Bicoid morphogen gradient requires protein movement from anteriorly localized mRNA. PLOS Biol. 9:3e1000596
     [Google Scholar]
124. Liu L, Nemashkalo A, Rezende L, Jung JY, Chhabra S et al. 2022. Nodal is a short-range morphogen with activity that spreads through a relay mechanism in human gastruloids. Nat. Commun. 13:1497
     [Google Scholar]
125. Lo W-C, Zhou S, Wan FY-M, Lander AD, Nie Q. 2015. Robust and precise morphogen-mediated patterning: trade-offs, constraints and mechanisms. J. R. Soc. Interface 12:10220141041
     [Google Scholar]
126. Lord ND, Carte AN, Abitua PB, Schier AF. 2021. The pattern of nodal morphogen signaling is shaped by co-receptor expression. eLife 10:e54894
     [Google Scholar]
127. Ma Y, Erkner A, Gong R, Yao S, Taipale J et al. 2002. Hedgehog-mediated patterning of the mammalian embryo requires transporter-like function of dispatched. Cell 111:163–75
     [Google Scholar]
128. Macdonald PM, Struhl G. 1986. A molecular gradient in early Drosophila embryos and its role in specifying the body pattern. Nature 324:537–45
     [Google Scholar]
129. Mähönen AP, Ten Tusscher K, Siligato R, Smetana O, Díaz-Triviño S et al. 2014. PLETHORA gradient formation mechanism separates auxin responses. Nature 515:7525125–29
     [Google Scholar]
130. Manu Surkova S, Spirov AV, Gursky VV, Janssens H et al. 2009. Canalization of gene expression in the Drosophila blastoderm by gap gene cross regulation. PLOS Biol. 7:3e1000049
     [Google Scholar]
131. Mateus R, Holtzer L, Seum C, Hadjivasiliou Z, Dubois M et al. 2020. BMP signaling gradient scaling in the zebrafish pectoral fin. Cell Rep. 30:124292–302.e7
     [Google Scholar]
132. Matsuda S, Schaefer JV, Mii Y, Hori Y, Bieli D et al. 2021. Asymmetric requirement of Dpp/BMP morphogen dispersal in the Drosophila wing disc. Nat. Commun. 12:6435
     [Google Scholar]
133. Mattes B, Dang Y, Greicius G, Kaufmann LT, Prunsche B et al. 2018. Wnt/PCP controls spreading of Wnt/β-catenin signals by cytonemes in vertebrates. eLife 7:e36953
     [Google Scholar]
134. Matusek T, Wendler F, Polès S, Pizette S, D'Angelo G et al. 2014. The ESCRT machinery regulates the secretion and long-range activity of Hedgehog. Nature 516:752999–103
     [Google Scholar]
135. McGough IJ, Vecchia L, Bishop B, Malinauskas T, Beckett K et al. 2020. Glypicans shield the Wnt lipid moiety to enable signalling at a distance. Nature 585:782385–90
     [Google Scholar]
136. Melen GJ, Levy S, Barkai N, Shilo B-Z. 2005. Threshold responses to morphogen gradients by zero-order ultrasensitivity. Mol. Syst. Biol. 1:2005.0028
     [Google Scholar]
137. Merino MM, Seum C, Dubois M, Gonzalez-Gaitan M. 2022. A role for Flower and cell death in controlling morphogen gradient scaling. Nat. Cell Biol. 24:4424–33
     [Google Scholar]
138. Míguez DG, Iannini A, García-Morales D, Casares F. 2022. The effects of Hh morphogen source movement on signaling dynamics. Development 149:23dev199842
     [Google Scholar]
139. Mihara E, Hirai H, Yamamoto H, Tamura-Kawakami K, Matano M et al. 2016. Active and water-soluble form of lipidated Wnt protein is maintained by a serum glycoprotein afamin/α-albumin. eLife 5:e11621
     [Google Scholar]
140. Mir M, Stadler MR, Ortiz SA, Hannon CE, Harrison MM et al. 2018. Dynamic multifactor hubs interact transiently with sites of active transcription in Drosophila embryos. eLife 7:e40497
     [Google Scholar]
141. Mizutani CM, Meyer N, Roelink H, Bier E. 2006. Threshold-dependent BMP-mediated repression: a model for a conserved mechanism that patterns the neuroectoderm. PLOS Biol. 4:10e313
     [Google Scholar]
142. Mlodzik M, Gehring WJ. 1987. Expression of the caudal gene in the germ line of Drosophila: formation of an RNA and protein gradient during early embryogenesis. Cell 48:3465–78
     [Google Scholar]
143. Morishita Y, Iwasa Y. 2009. Accuracy of positional information provided by multiple morphogen gradients with correlated noise. Phys. Rev. E Stat. Nonlin. Soft. Matter Phys. 79:6, Part 1061905
     [Google Scholar]
144. Müller 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 336:6082721–24
     [Google Scholar]
145. Müller P, Rogers KW, Yu SR, Brand M, Schier AF. 2013. Morphogen transport. Development 140:81621–38
     [Google Scholar]
146. Mulligan KA, Fuerer C, Ching W, Fish M, Willert K, Nusse R. 2012. Secreted Wingless-interacting molecule (Swim) promotes long-range signaling by maintaining Wingless solubility. PNAS 109:2370–77
     [Google Scholar]
147. Nakato H, Li J-P. 2016. Functions of heparan sulfate proteoglycans in development: insights from Drosophila models. Int. Rev. Cell Mol. Biol. 325:275–93
     [Google Scholar]
148. Nugent MA, Edelman ER. 1992. Kinetics of basic fibroblast growth factor binding to its receptor and heparan sulfate proteoglycan: a mechanism for cooperactivity. Biochemistry 31:378876–83
     [Google Scholar]
149. Ochoa-Espinosa A, Yucel G, Kaplan L, Pare A, Pura N et al. 2005. The role of binding site cluster strength in Bicoid-dependent patterning in Drosophila. PNAS 102:144960–65
     [Google Scholar]
150. Oginuma M, Moncuquet P, Xiong F, Karoly E, Chal J et al. 2017. A gradient of glycolytic activity coordinates FGF and Wnt signaling during elongation of the body axis in amniote embryos. Dev. Cell 40:4342–53.e10
     [Google Scholar]
151. Ohkawara B, Iemura S, ten Dijke P, Ueno N. 2002. Action range of BMP is defined by its N-terminal basic amino acid core. Curr. Biol. 12:3205–9
     [Google Scholar]
152. Oosterveen T, Kurdija S, Alekseenko Z, Uhde CW, Bergsland M et al. 2012. Mechanistic differences in the transcriptional interpretation of local and long-range Shh morphogen signaling. Dev. Cell 23:51006–19
     [Google Scholar]
153. Panáková D, Sprong H, Marois E, Thiele C, Eaton S. 2005. Lipoprotein particles are required for Hedgehog and Wingless signalling. Nature 435:703858–65
     [Google Scholar]
154. Pankratz MJ, Busch M, Hoch M, Seifert E, Jäckle H. 1992. Spatial control of the gap gene knirps in the Drosophila embryo by posterior morphogen system. Science 255:5047986–89
     [Google Scholar]
155. Panovska-Griffiths J, Page KM, Briscoe J. 2013. A gene regulatory motif that generates oscillatory or multiway switch outputs. J. R. Soc. Interface 10:7920120826
     [Google Scholar]
156. Parker J, Struhl G. 2020. Control of Drosophila wing size by morphogen range and hormonal gating. PNAS 117:5031935–44
     [Google Scholar]
157. Patel A, Wu Y, Han X, Su Y, Maugel T et al. 2022. Cytonemes coordinate asymmetric signaling and organization in the Drosophila muscle progenitor niche. Nat. Commun. 13:11185
     [Google Scholar]
158. Perez-Carrasco R, Barnes CP, Schaerli Y, Isalan M, Briscoe J, Page KM. 2018. Combining a toggle switch and a repressilator within the AC-DC circuit generates distinct dynamical behaviors. Cell Syst. 6:4521–30.e3
     [Google Scholar]
159. Perez-Carrasco R, Guerrero P, Briscoe J, Page KM. 2016. Intrinsic noise profoundly alters the dynamics and steady state of morphogen-controlled bistable genetic switches. PLOS Comput. Biol. 12:10e1005154
     [Google Scholar]
160. Perry MW, Boettiger AN, Levine M. 2011. Multiple enhancers ensure precision of gap gene-expression patterns in the Drosophila embryo. PNAS 108:3313570–75
     [Google Scholar]
161. Peterson KA, Nishi Y, Ma W, Vedenko A, Shokri L et al. 2012. Neural-specific Sox2 input and differential Gli-binding affinity provide context and positional information in Shh-directed neural patterning. Genes Dev. 26:242802–16
     [Google Scholar]
162. Petkova MD, Tkačik G, Bialek W, Wieschaus EF, Gregor T. 2019. Optimal decoding of cellular identities in a genetic network. Cell 176:4844–55.e15
     [Google Scholar]
163. Pezzotta A, Briscoe J. 2022. Optimal control of gene regulatory networks for morphogen-driven tissue patterning. bioRxiv 2022.07.26.501519. https://doi.org/10.1101/2022.07.26.501519
164. Pfeiffer S, Alexandre C, Calleja M, Vincent JP. 2000. The progeny of wingless-expressing cells deliver the signal at a distance in Drosophila embryos. Curr. Biol. 10:6321–24
     [Google Scholar]
165. Pinheiro D, Kardos R, Hannezo É, Heisenberg C-P. 2022. Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming. Nat. Phys. 18:121482–93
     [Google Scholar]
166. Pomreinke AP, Soh GH, Rogers KW, Bergmann JK, Bläßle AJ, Müller P. 2017. Dynamics of BMP signaling and distribution during zebrafish dorsal-ventral patterning. eLife 6:e25861
     [Google Scholar]
167. Rahimi N, Carmon S, Averbukh I, Khajouei F, Sinha S et al. 2020. Global shape of Toll activation is determined by wntD enhancer properties. PNAS 117:31552–58
     [Google Scholar]
168. Raj A, van Oudenaarden A. 2008. Nature, nurture, or chance: stochastic gene expression and its consequences. Cell 135:2216–26
     [Google Scholar]
169. Ramel M-C, Hill CS. 2013. The ventral to dorsal BMP activity gradient in the early zebrafish embryo is determined by graded expression of BMP ligands. Dev. Biol. 378:2170–82
     [Google Scholar]
170. Ramírez-Weber FA, Kornberg TB. 1999. Cytonemes: cellular processes that project to the principal signaling center in Drosophila imaginal discs. Cell 97:5599–607
     [Google Scholar]
171. Raser JM, O'Shea EK 2005. Noise in gene expression: origins, consequences, and control. Science 309:57432010–13
     [Google Scholar]
172. Rasolonjanahary M, Vasiev B. 2016. Scaling of morphogenetic patterns in reaction-diffusion systems. J. Theor. Biol. 404:109–19
     [Google Scholar]
173. Romanova-Michaelides M, Hadjivasiliou Z, Aguilar-Hidalgo D, Basagiannis D, Seum C et al. 2022. Morphogen gradient scaling by recycling of intracellular Dpp. Nature 602:7896287–93
     [Google Scholar]
174. Roy S, Huang H, Liu S, Kornberg TB. 2014. Cytoneme-mediated contact-dependent transport of the Drosophila decapentaplegic signaling protein. Science 343:61731244624
     [Google Scholar]
175. Rudolf K, Umetsu D, Aliee M, Sui L, Jülicher F, Dahmann C. 2015. A local difference in Hedgehog signal transduction increases mechanical cell bond tension and biases cell intercalations along the Drosophila anteroposterior compartment boundary. Development 142:223845–58
     [Google Scholar]
176. Sáez M, Blassberg R, Camacho-Aguilar E, Siggia ED, Rand DA, Briscoe J. 2022. Statistically derived geometrical landscapes capture principles of decision-making dynamics during cell fate transitions. Cell Syst. 13:112–28.e3
     [Google Scholar]
177. Sako K, Pradhan SJ, Barone V, Inglés-Prieto Á, Müller P et al. 2016. Optogenetic control of nodal signaling reveals a temporal pattern of nodal signaling regulating cell fate specification during gastrulation. Cell Rep. 16:3866–77
     [Google Scholar]
178. Sanders TA, Llagostera E, Barna M. 2013. Specialized filopodia direct long-range transport of SHH during vertebrate tissue patterning. Nature 497:7451628–32
     [Google Scholar]
179. Schaerli Y, Munteanu A, Gili M, Cotterell J, Sharpe J, Isalan M. 2014. A unified design space of synthetic stripe-forming networks. Nat. Commun. 5:4905
     [Google Scholar]
180. Shimizu K, Gurdon JB. 1999. A quantitative analysis of signal transduction from activin receptor to nucleus and its relevance to morphogen gradient interpretation. PNAS 96:126791–96
     [Google Scholar]
181. Shimmi O, Umulis D, Othmer H, O'Connor MB 2005. Facilitated transport of a Dpp/Scw heterodimer by Sog/Tsg leads to robust patterning of the Drosophila blastoderm embryo. Cell 120:6873–86
     [Google Scholar]
182. Shvartsman SY, Baker RE. 2012. Mathematical models of morphogen gradients and their effects on gene expression: mathematical models of morphogen gradients. WIREs Dev. Biol. 1:5715–30
     [Google Scholar]
183. Shyer AE, Huycke TR, Lee C, Mahadevan L, Tabin CJ. 2015. Bending gradients: how the intestinal stem cell gets its home. Cell 161:3569–80
     [Google Scholar]
184. Simsek MF, Chandel AS, Saparov D, Zinani OQH, Clason N, Özbudak EM. 2023. Periodic inhibition of Erk activity drives sequential somite segmentation. Nature 613:7942153–59
     [Google Scholar]
185. Simsek MF, Özbudak EM. 2022. Patterning principles of morphogen gradients. Open Biol. 12:10220224
     [Google Scholar]
186. Sokolowski TR, Erdmann T, ten Wolde PR. 2012. Mutual repression enhances the steepness and precision of gene expression boundaries. PLOS Comput. Biol. 8:8e1002654
     [Google Scholar]
187. Sorre B, Warmflash A, Brivanlou AH, Siggia ED. 2014. Encoding of temporal signals by the TGF-β pathway and implications for embryonic patterning. Dev. Cell 30:3334–42
     [Google Scholar]
188. Stanganello E, Hagemann AIH, Mattes B, Sinner C, Meyen D et al. 2015. Filopodia-based Wnt transport during vertebrate tissue patterning. Nat. Commun. 6:5846
     [Google Scholar]
189. Stapornwongkul KS, de Gennes M, Cocconi L, Salbreux G, Vincent J-P. 2020. Patterning and growth control in vivo by an engineered GFP gradient. Science 370:6514321–27
     [Google Scholar]
190. Stapornwongkul KS, Vincent J-P. 2021. Generation of extracellular morphogen gradients: the case for diffusion. Nat. Rev. Genet. 22:6393–411
     [Google Scholar]
191. Steward R, Zusman SB, Huang LH, Schedl P. 1988. The dorsal protein is distributed in a gradient in early Drosophila embryos. Cell 55:3487–95
     [Google Scholar]
192. Teimouri H, Kolomeisky AB. 2015. The role of source delocalization in the development of morphogen gradients. Phys. Biol. 12:2026006
     [Google Scholar]
193. Tenzen T, Allen BL, Cole F, Kang J-S, Krauss RS, McMahon AP. 2006. The cell surface membrane proteins Cdo and Boc are components and targets of the Hedgehog signaling pathway and feedback network in mice. Dev. Cell 10:5647–56
     [Google Scholar]
194. The I, Bellaiche Y, Perrimon N. 1999. Hedgehog movement is regulated through tout velu-dependent synthesis of a heparan sulfate proteoglycan. Mol. Cell 4:4633–39
     [Google Scholar]
195. Tkačik G, Gregor T. 2021. The many bits of positional information. Development 148:2dev176065
     [Google Scholar]
196. Tsai TY-C, Sikora M, Xia P, Colak-Champollion T, Knaut H et al. 2020. An adhesion code ensures robust pattern formation during tissue morphogenesis. Science 370:6512113–16
     [Google Scholar]
197. Tuazon FB, Wang X, Andrade JL, Umulis D, Mullins MC. 2020. Proteolytic restriction of chordin range underlies BMP gradient formation. Cell Rep. 32:7108039
     [Google Scholar]
198. Tukachinsky H, Kuzmickas RP, Jao CY, Liu J, Salic A. 2012. Dispatched and Scube mediate the efficient secretion of the cholesterol-modified hedgehog ligand. Cell Rep. 2:2308–20
     [Google Scholar]
199. Umulis D, O'Connor MB, Blair SS 2009. The extracellular regulation of bone morphogenetic protein signaling. Development 136:223715–28
     [Google Scholar]
200. Umulis DM, Othmer HG. 2013. Mechanisms of scaling in pattern formation. Development 140:244830–43
     [Google Scholar]
201. Umulis DM, Othmer HG. 2015. The role of mathematical models in understanding pattern formation in developmental biology. Bull. Math. Biol. 77:5817–45
     [Google Scholar]
202. Verd B, Clark E, Wotton KR, Janssens H, Jiménez-Guri E et al. 2018. A damped oscillator imposes temporal order on posterior gap gene expression in Drosophila. PLOS Biol. 16:2e2003174
     [Google Scholar]
203. Vuilleumier R, Springhorn A, Patterson L, Koidl S, Hammerschmidt M et al. 2010. Control of Dpp morphogen signalling by a secreted feedback regulator. Nat. Cell Biol. 12:6611–17
     [Google Scholar]
204. Vyas N, Walvekar A, Tate D, Lakshmanan V, Bansal D et al. 2014. Vertebrate Hedgehog is secreted on two types of extracellular vesicles with different signaling properties. Sci. Rep. 4:7357
     [Google Scholar]
205. Warmflash A, Zhang Q, Sorre B, Vonica A, Siggia ED, Brivanlou AH. 2012. Dynamics of TGF-β signaling reveal adaptive and pulsatile behaviors reflected in the nuclear localization of transcription factor Smad4. PNAS 109:28E1947–56
     [Google Scholar]
206. Wartlick O, Jülicher F, Gonzalez-Gaitan M. 2014. Growth control by a moving morphogen gradient during Drosophila eye development. Development 141:91884–93
     [Google Scholar]
207. Wartlick O, Kicheva A, González-Gaitán M. 2009. Morphogen gradient formation. Cold Spring Harb. Perspect. Biol. 1:3a001255
     [Google Scholar]
208. Wartlick O, Mumcu P, Kicheva A, Bittig T, Seum C et al. 2011. Dynamics of Dpp signaling and proliferation control. Science 331:60211154–59
     [Google Scholar]
209. Wharton SJ, Basu SP, Ashe HL. 2004. Smad affinity can direct distinct readouts of the embryonic extracellular Dpp gradient in Drosophila. Curr. Biol. 14:171550–58
     [Google Scholar]
210. Wierbowski BM, Petrov K, Aravena L, Gu G, Xu Y, Salic A. 2020. Hedgehog pathway activation requires coreceptor-catalyzed, lipid-dependent relay of the Sonic hedgehog ligand. Dev. Cell 55:4450–67.e8
     [Google Scholar]
211. Woods IG, Talbot WS. 2005. The you gene encodes an EGF-CUB protein essential for Hedgehog signaling in zebrafish. PLOS Biol. 3:3e66
     [Google Scholar]
212. Wu H, Manu JR, Ma J. 2015. Temporal and spatial dynamics of scaling-specific features of a gene regulatory network in Drosophila. Nat. Commun. 6:110031
     [Google Scholar]
213. Xiong F, Tentner AR, Huang P, Gelas A, Mosaliganti KR et al. 2013. Specified neural progenitors sort to form sharp domains after noisy Shh signaling. Cell 153:3550–61
     [Google Scholar]
214. Yayon A, Klagsbrun M, Esko JD, Leder P, Ornitz DM. 1991. Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor. Cell 64:4841–48
     [Google Scholar]
215. Yu D, Small S. 2008. Precise registration of gene expression boundaries by a repressive morphogen in Drosophila. Curr. Biol. 18:12868–76
     [Google Scholar]
216. Zagorski M, Tabata Y, Brandenberg N, Lutolf MP, Tkačik G et al. 2017. Decoding of position in the developing neural tube from antiparallel morphogen gradients. Science 356:63451379–83
     [Google Scholar]
217. Zecca M, Basler K, Struhl G. 1995. Sequential organizing activities of engrailed, hedgehog and decapentaplegic in the Drosophila wing. Development 121:2265–78
     [Google Scholar]
218. Zeng X, Goetz JA, Suber LM, Scott WJ, Schreiner CM, Robbins DJ. 2001. A freely diffusible form of Sonic hedgehog mediates long-range signalling. Nature 411:6838716–20
     [Google Scholar]
219. Zhu J, Nakamura E, Nguyen M-T, Bao X, Akiyama H, Mackem S. 2008. Uncoupling Sonic hedgehog control of pattern and expansion of the developing limb bud. Dev. Cell 14:4624–32
     [Google Scholar]
220. Zhu Y, Qiu Y, Chen W, Nie Q, Lander AD. 2020. Scaling a Dpp morphogen gradient through feedback control of receptors and co-receptors. Dev. Cell 53:6724–39.e14
     [Google Scholar]
221. Zinski J, Bu Y, Wang X, Dou W, Umulis D, Mullins MC. 2017. Systems biology derived source-sink mechanism of BMP gradient formation. eLife 6:e22199
     [Google Scholar]