Genetics of morphogen gradients

Nature Reviews Genetics

Volumn 2, Issue 8, 2001, Pages 620-630

  Tabata, Tetsuya ^a  

^a UNIVERSITY OF TOKYO   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

DROSOPHILA MELANOGASTER; MELANOGASTER;

ANIMAL; DROSOPHILA MELANOGASTER; GENE EXPRESSION REGULATION; GENETICS; MORPHOGENESIS; PHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; BODY PATTERNING; DROSOPHILA MELANOGASTER; GENE EXPRESSION REGULATION, DEVELOPMENTAL; MORPHOGENESIS; SIGNAL TRANSDUCTION;

EID: 0035434660     PISSN: 14710056     EISSN: None     Source Type: Journal    
DOI: 10.1038/35084577     Document Type: Review

References (101)

1. Wolpert, L. Positional information and the spatial pattern of cellular differentiation. J. Theor. Biol. 25, 1-47 (1969).
2. Turing, A. M. The chemical basis of morphogenesis. Phil. Trans. R. Soc. Lond. B 237, 37-72 (1952).
3. Gurdon, J. B., Harger, P., Mitchell, A. & Lemaire, P. Activin signalling and response to a morphogen gradient. Nature 371, 487-492 (1994).
4. Jones, C. M., Armes, N. & Smith, J. C. Signaling by TGF-β family members: short-range effects of Xnr-2 and BMP-4 contrast with the long-range effects of activin. Curr. Biol. 6, 1468-1475 (1996).
5. Dosch, R., Gawantka, V., Delius, H., Blumenstock, C. & Niehrs, C. Bmp-4 acts as a morphogen in dorsoventral mesoderm patterning in Xenopus. Development 124, 2325-2334 (1997).
6. Ericson, J., Briscoe, J., Rashbass, P., Van Heyningen, V. & Jessell, T. M. Graded sonic hedgehog signaling and the specification of cell fate in the ventral neural tube. Cold Spring Harb. Symp. Quant. Biol. 62, 451-466 (1997).
7. Lee, K. J. & Jessell, T. M. The specification of dorsal cell fates in the vertebrate central nervous system. Annu. Rev. Neurosci. 22, 261-294 (1999).
8. Lee, K. J., Dietrich, P. & Jessell, T. M. Genetic ablation reveals that the roof plate is essential for dorsal interneuron specification. Nature 403, 734-740 (2000).
9. Irving, C. & Mason, I. Signalling by FGF8 from the isthmus patterns anterior hindbrain and establishes the anterior limit of Hox gene expression. Development 127, 177-186 (2000).
10. Crossley, P. H., Martinez, S. & Martin, G. R. Midbrain development induced by FGFB in the chick embryo. Nature 380, 65-68 (1995).
11. Martinez, S., Crossley, P. H., Cobos, I., Rubenstein, J. L. & Martin, G. R. FGF8 induces formation of an ectopic isthmic organizer and isthmocerebellar development via a repressive effect on Otx2 expression. Development 126, 1189-1200 (1999).
12. Garcia-Bellido, A., Ripoll, P. & Morata, G. Developmental compartmentalisation of the wing disk of Drosophila. Nature New Biol. 245, 251-253 (1973).
13. Garcia-Bellido, A., Ripoll, P. & Morata, G. Developmental compartmentalization in the dorsal mesothoracic disc of Drosophila. Dev. Biol. 48, 132-147 (1976).
14. McNeill, H. Sticking together and sorting things out: adhesion as a force in development. Nature Rev. Genet. 1, 100-108 (2000).
15. Simmonds, A. J., Brook, W. J., Cohen, S. M. & Bell, J. B. Distinguishable functions for engrailed and invected in anterior-posterior patterning in the Drosophila wing. Nature 376, 424-427 (1995).
16. Guillen, I. et al. The function of engrailed and the specification of Drosophila wing pattern. Development 121, 3447-3456 (1995).
17. Tabata, T., Schwartz, C., Gustavson, E., Ali, Z. & Kornberg, T. B. Creating a Drosophila wing de novo, the role of engrailed, and the compartment border hypothesis. Development 121, 3359-3369 (1995). Shows that the anteroposterior compartment boundary functions as the organizing centre that patterns the complete wing.
18. Tabata, T. & Kornberg, T. B. Hedgehog is a signaling protein with a key role in patterning Drosophila imaginal discs. Cell 76, 89-102 (1994).
19. Mullor, J. L., Calleja, M., Capdevila, J. & Guerrero, I. Hedgehog activity, independent of decapentaplegic, participates in wing disc patterning. Development 124, 1227-1237 (1997).
20. Strigini, M. & Cohen, S. M. A Hedgehog activity gradient contributes to AP axial patterning of the Drosophila wing. Development 124, 4697-4705 (1997).
21. Capdevila, J. & Guerrero, I. Targeted expression of the signaling molecule decapentaplegic induces pattern duplications and growth alterations in Drosophila wings. EMBO J. 13, 4459-4468 (1994).
22. Basler, K. & Struhl, G. Compartment boundaries and the control of Drosophila limb pattern by Hedgehog protein. Nature 368, 208-214 (1994). Landmark paper showing that the Hedgehog protein can Induce the complete duplication of the anterior compartment of Drosophila limbs.
23. Zecca, M., Basler, K. & Struhl, G. Sequential organizing activities of engrailed, hedgehog and decapentaplegic in the Drosophila wing. Development 121, 2265-2278 (1995). Shows that Decapentaplegic has an organizing activity that patterns the whole wing except for the central domain.
24. Lecuit, T. et al. Two distinct mechanisms for long-range patterning by Decapentaplegic in the Drosophila wing. Nature 381, 387-393 (1996).
25. Neuen, D., Burke, R., Struhl, G. & Basler, K. Direct and long-range action of a DPP morphogen gradient. Cell 85, 357-368 (1996). With reference 24, this paper showed for the first time that Decapentaplegic (Dpp) functions as a long-range signalling molecule. Reference 25 also shows that Dpp regulates different target genes in a concentration-dependent manner.
26. Irvine, K. D. & Wieschaus, E. Fringe, a boundary-specific signaling molecule, mediates interactions between dorsal and ventral cells during Drosophila wing development. Cell 79, 595-606 (1994).
27. Diaz-Benjumea, F. J. & Cohen, S. M. Interaction between dorsal and ventral cells in the imaginai disc directs wing development in Drosophila. Cell 75, 741-752 (1993).
28. Kim, J., Irvine, K. D. & Carroll, S. B. Cell recognition, signal induction, and symmetrical gene activation at the dorsal-ventral boundary of the developing Drosophila wing. Cell 82, 795-802 (1995).
29. Doherty, D., Feger, G., Younger-Shepherd, S., Jan, L. Y. & Jan, Y. N. Delta is a ventral to dorsal signal complementary to Serrate, another Notch ligand, in Drosophila wing formation. Genes Dev. 10, 421-434 (1996).
30. Neumann, C. J. & Cohen, S. M. A hierarchy of cross-regulation involving Notch, Wingless, Vestigial and Cut organizes the dorsal/ventral axis of the Drosophila wing. Development 122, 3477-3485 (1996).
31. Zecca, M., Basler, K. & Struhl, G. Direct and long-range action of a Wingless morphogen gradient. Cell 87, 833-844 (1996).
32. Neumann, C. J. & Cohen, S. M. Long-range action of Wingless organizes the dorsal-ventral axis of the Drosophila wing. Development 124, 871-880 (1997).
33. Massague, J. How cells read TGF-β signals. Nature Rev. Mol. Cell Biol. 1, 169-178 (2000).
34. Chiang, C. et al. Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 383, 407-413 (1996).
35. Briscoe, J., Chen, Y., Jessell, T. M. & Struhl, G. A Hedgehog-insensitive form of Patched provides evidence for direct long-range morphogen activity of Sonic Hedgehog in the neural tube. Mol. Cell 7, 1279-1291 (2001).
36. Lewis, P. M. et al. Cholesterol modification of sonic hedgehog is required for long-range signaling activity and effective modulation of signaling by ptc1. Cell 105, 599-612 (2001).
37. Chen, Y. & Schier, A. F. The zebrafish nodal signal Squint functions as a morphogen. Nature 411, 607-610 (2001). Provides the first unambiguous evidence that a signalling molecule (Squint) functions as a morphogen in vertebrate embryogenesis.
38. Teleman, A. A. & Cohen, S. M. Dpp gradient formation in the Drosophila wing imaginal disc. Cell 103, 971-980 (2000).
39. Entchev, E. V., Schwabedissen, A. & Gonzalez-Gaitan, M. Gradient formation of the TGF-β homolog Dpp. Cell 103, 981-991 (2000). With reference 38, this paper visualizes the Decapentaplegic (Dpp) gradient in vivo by using a Dpp-GFP fusion protein as a marker. Reference 39 also shows that endocytic transport is important in generating the Dpp gradient.
40. Lecuit, T. & Cohen, S. M. Dpp receptor levels contribute to shaping the Dpp morphogen gradient in the Drosophila wing imaginai disc. Development 125, 4901-4907 (1998).
41. Bejsovec, A. & Wieschaus, E. Signaling activities of the Drosophila wingless gene are separately mutable and appear to be transduced at the cell surface. Genetics 139, 309-320 (1995).
42. Seugnet, L., Simpson, P. & Haenlin, M. Requirement for Dynamin during Notch signaling in Drosophila neurogenesis. Dev. Biol. 192, 585-598 (1997).
43. Vieira, A. V., Lamaze, C. & Schmid, S. L. Control of EGF receptor signaling by clathrin-mediated endocytosis. Science 274, 2086-2089 (1996).
44. Gonzalez-Gaitan, M. & Jackle, H. The range of spalt-activating Dpp signalling is reduced in endocytosis-defective Drosophila wing discs. Mech. Dev. 87, 143-151 (1999).
45. Moline, M. M., Southern, C. & Bejsovec, A. Directionality of Wingless protein transport influences epidermal patterning in the Drosophila embryo. Development 126, 4375-4384 (1999).
46. Strigini, M. & Cohen, S. M. Wingless gradient formation in the Drosophila wing. Curr. Biol. 10, 293-300 (2000).
47. Ingham, P. W. Transducing Hedgehog: the story so far. EMBO J. 17, 3505-3511 (1998).
48. Denef, N., Neubuser, D., Perez, L. & Cohen, S. M. Hedgehog induces opposite changes in turnover and subcellular localization of Patched and Smoothened. Cell 102, 521-531 (2000).
49. Alcedo, J., Zou, Y. & Noll, M. Posttranscriptional regulation of smoothened is part of a self-correcting mechanism in the Hedgehog signaling system. Mol. Cell 6, 457-465 (2000).
50. Martin, V., Carrillo, G., Torroja, C. & Guerrero, I. The sterol-sensing domain of Patched protein seems to control Smoothened activity through Patched vesicular trafficking. Curr. Biol. 11, 601-607 (2001).
51. Kjellen, L. & Lindahl, U. Proteoglycans: structures and interactions. Annu. Rev. Biochem. 60, 443-475 (1991).
52. Hacker, U., Lin, X. & Perrimon, N. The Drosophila sugarless gene modulates Wingless signaling and encodes an enzyme involved in polysaccharide biosynthesis. Development 124, 3565-3573 (1997).
53. Binari, R. C. et al. Genetic evidence that heparin-like glycosaminoglycans are involved in wingless signaling. Development 124, 2623-2632 (1997).
54. Haerry, T. E., Heslip, T. R., Marsh, J. L. & O'Connor, M. B. Defects in glucuronate biosynthesis disrupt Wingless signaling in Drosophila. Development 124, 3055-3064 (1997).
55. Tsuda, M. et al. The cell-surface proteoglycan Dally regulates Wingless signalling in Drosophila. Nature 400, 276-280 (1999).
56. Lin, X. & Perrimon, N. Dally cooperates with Drosophila Frizzled 2 to transduce Wingless signalling. Nature 400, 281-284 (1999).
57. Baeg, G. H., Lin, X., Khare, N., Baumgartner, S. & Perrimon, N. Heparan sulfate proteoglycans are critical for the organization of the extracellular distribution of Wingless. Development 128, 87-94 (2001). Together with references 62 and 64, this paper shows that heparan sulphate proteoglycans are involved in regulating morphogen movement
58. Porter, J. A. et al. The product of Hedgehog autoproteolytic cleavage active in local and long-range signalling. Nature 374, 363-366 (1995).
59. Porter, J. A., Young, K. E. & Beachy, P. A. Cholesterol modification of Hedgehog signaling proteins in animal development. Science 274, 255-259 (1996).
60. Porter, J. A. et al. Hedgehog patterning activity: role of a lipophilic modification mediated by the carboxy-terminal autoprocessing domain. Cell 86, 21-34 (1996).
61. Burke, R. et al. Dispatched, a novel sterol-sensing domain protein dedicated to the release of cholesterol-modified Hedgehog from signaling cells. Cell 99, 803-815 (1999).
62. Bellaiche, Y., The, I. & Perrimon, N. Tout-velu is a Drosophila homologue of the putative tumour suppressor EXT-1 and is needed for Hh diffusion. Nature 394, 85-88 (1998).
63. The, I., Bellaiche, Y. & Perrimon, N. Hedgehog movement is regulated through tout velu-dependent synthesis of a heparan sulfate proteoglycan. Mol. Cell 4, 633-639 (1999).
64. Senay, C. et al. The EXT1/EXT2 tumor suppressors: catalytic activities and role in heparan sulfate biosynthesis. EMBO Rep. 1, 282-286 (2000).
65. Ahn, J. et al. Cloning of the putative tumour suppressor gene for hereditary multiple exostoses (EXT1). Nature Genet. 11, 137-143 (1995).
66. Stickens, D. et al. The EXT2 multiple exostoses gene defines a family of putative tumour suppressor genes. Nature Genet. 14, 25-32 (1996).
67. Vortkamp, A. et al. Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein. Science 273, 613-622 (1996).
68. St-Jacques, B., Hammerschmidt, M. & McMahon, A. P. Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation. Genes Dev. 13, 2072-2086 (1999).
69. Lin, X. et al. Disruption of gastrulation and heparan sulfate biosynthesis in EXT1-deficient mice. Dev. Biol. 224, 299-311 (2000).
70. Tanimoto, H., Itoh, S., ten Dijke, P. & Tabata, T. Hedgehog creates a gradient of DPP activity in Drosophila wing imaginal discs. Mol. Cell 5, 59-71 (2000). The activity gradient of Decapentaplegic (Dpp) is visualized by using an antibody that recognizes a phosphorylated form of the Mothers against Dpp protein, a cytoplasmic signal transducer of Dpp signalling.
71. Tsuneizumi, K. et al. Daughters against Dpp modulates Dpp organizing activity in Drosophila wing development. Nature 389, 627-631 (1997). Shows that the activity gradient of Decapentaplegic (Dpp) is regulated by a negative-feedback loop mediated by the Daughters against Dpp protein.
72. Funakoshi, Y., Minami, M. & Tabata, T. mtv shapes the activity gradient of the Dpp morphogen through regulation of thick veins. Development 128, 67-74 (2001).
73. Chen, Y. & Struhl, G. Dual roles for Patched in sequestering and transducing Hedgehog. Cell 87, 553-563 (1996). Shows that Patched restricts the movement of its ligand, Hedgehog, and regulates its range of action.
74. Bhanot, P. et al. A new member of the frizzled family from Drosophila functions as a Wingless receptor. Nature 382, 225-230 (1996).
75. Sato, A., Kojima, T., Ui-Tei, K., Miyata, Y. & Saigo, K. Dfrizzled-3, a new Drosophila Wnt receptor, acting as an attenuator of Wingless signaling in wingless hypomorphic mutants. Development 126, 4421-4430 (1999).
76. Chen, C. M. & Struhl, G. Wingless transduction by the Frizzled and Frizzled2 proteins of Drosophila. Development 126, 5441-5452 (1999).
77. Cadigan, K. M., Fish, M. P., Rulifson, E. J. & Nusse, R. Wingless repression of Drosophila frizzled 2 expression shapes the Wingless morphogen gradient in the wing. Cell 93, 767-777 (1998).
78. Marigo, V. & Tabin, C. J. Regulation of patched by Sonic hedgehog in the developing neural tube. Proc. Natl Acad. Sci. USA 93, 9346-9351 (1996).
79. Marigo, V., Scott, M. P., Johnson, R. L., Goodrich, L. V. & Tabin, C. J. Conservation in hedgehog signaling: induction of a chicken patched homolog by Sonic hedgehog in the developing limb. Development 122, 1225-1233 (1996).
80. Campbell, G. & Tomlinson, A. Transducing the Dpp morphogen gradient in the wing of Drosophila: regulation of Dpp targets by brinker. Cell 96, 553-562 (1999).
81. Jazwinska, A., Kirov, N., Wieschaus, E., Roth, S. & Rushlow, C. The Drosophila gene brinker reveals a novel mechanism of Dpp target gene regulation. Cell 96, 563-573 (1999).
82. Minami, M., Kinoshita, N., Kamoshida, Y., Tanimoto, H. & Tabata, T. brinker is a target of Dpp in Drosophila that negatively regulates Dpp-dependent genes. Nature 398, 242-246 (1999).
83. Sivasankaran, R., Vigano, M. A. Muller, B., Affolter, M. & Basler, K. Direct transcriptional control of the Dpp target omb by the DNA binding protein Brinker. EMBO J. 19, 6162-6172 (2000).
84. Rushlow, C., Colosimo, P. F., Lin, M. C., Xu, M. & Kirov, N. Transcriptional regulation of the Drosophila gene zen by competing Smad and Brinker inputs. Genes Dev. 15, 340-351 (2001).
85. Kirkpatrick, H., Johnson, K. & Laughon, A. Repression of Dpp targets by binding of brinker to mad sites. J. Biol. Chem. 276, 18216-18222 (2001).
86. Aza-Blanc, P., Ramirez-Weber, F. A., Laget, M. P., Schwartz, C. & Komberg, T. B. Proteolysis that is inhibited by Hedgehog targets Cubitus interruptus protein to the nucleus and converts it to a repressor. Cell 89, 1043-1053 (1997).
87. Methot, N. & Basler, K. Hedgehog controls limb development by regulating the activities of distinct transcriptional activator and repressor forms of Cubitus interruptus. Cell 96, 819-831 (1999).
88. Chen, C. H. et al. Nuclear trafficking of Cubitus interruptus in the transcriptional regulation of Hedgehog target gene expression. Cell 98, 305-316 (1999).
89. Muller, B. & Basler, K. The repressor and activator forms of Cubitus interruptus control Hedgehog target genes through common generic gli-binding sites. Development 127, 2999-3007 (2000).
90. Brunner, E., Peter, O., Schweizer, L. & Basler, K. pangolin encodes a Lef-1 homologue that acts downstream of Armadillo to transduce the Wingless signal in Drosophila. Nature 385, 829-833 (1997).
91. Van de Wetering, M. et al. Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF. Cell 88, 789-799 (1997).
92. Cavallo, R. A. et al. Drosophila Tcf and Groucho interact to repress Wingless signalling activity. Nature 395, 604-608 (1998).
93. Ding, Q. et al. Mouse suppressor of fused is a negative regulator of sonic hedgehog signaling and alters the subcellular distribution of Gli1. Curr. Biol. 9, 1119-1122 (1999).
94. Wang, B., Fallon, J. F. & Beachy, P. A. Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb. Cell 100, 423-434 (2000).
95. Hecht, A. & Kemler, R. Curbing the nuclear activities of β-catenin. Control over Wnt target gene expression. EMBO Rep. 1, 24-28 (2000).
96. Roose, J. et al. The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors. Nature 395, 608-612 (1998).
97. Holley, S. A. et al. A conserved system for dorsal-ventral patterning in insects and vertebrates involving sog and chordin. Nature 376, 249-253 (1995).
98. Ramirez-Weber, F. A. & Komberg, T. B. Cytonemes: cellular processes that project to the principal signaling center in Drosophila imaginal discs. Cell 97, 599-607 (1999). This article reports that cells in Drosophila imaginai discs project cellular extensions called cytonemes to the anteroposterior compartment border, which functions as the organizing centre of the disc.
99. Golic, K. G. & Lindquist, S. The FLP recombinase of yeast catalyzes site-specific recombination in the Drosophila genome. Cell 59, 499-509 (1989).
100. Xu, T. & Rubin, G. M. Analysis of genetic mosaics in developing and adult Drosophila tissues. Development 117, 1223-1237 (1993).
101. Hama, C., Ali, Z. & Kornberg, T. B. Region-specific recombination and expression are directed by portions of the Drosophila engrailed promoter. Genes Dev. 4, 1079-1093 (1990).