Dorsal-ventral signaling in limb development

Current Opinion in Cell Biology

Volumn 9, Issue 6, 1997, Pages 867-876

  Irvine, Kenneth D ^a   Vogt, Thomas F ^b  

^a RUTGERS UNIVERSITY   (United States)

^b PRINCETON UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CELL INTERACTION; CELLULAR DISTRIBUTION; CHICKEN; DROSOPHILA; FEEDBACK SYSTEM; FORELIMB; LIMB DEVELOPMENT; NONHUMAN; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; VERTEBRATE;

EID: 0030722165     PISSN: 09550674     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0955-0674(97)80090-7     Document Type: Article

References (71)

1. Meinhardt H: Cell determination boundaries as organizing regions for secondary embryonic fields. Dev Biol 1983, 96:375-385.
2. French V, Bryant PJ, Bryant SV: Pattern regulation in epimorphic fields. Science 1976, 193:969-981.
3. Brook WJ, Diaz-Benjumea FJ, Cohen SM: Organizing spatial pattern in limb development. Annu Rev Cell Dev Biol 1996, 12:161-180.
4. Johnson RL, Tabin CJ: Molecular models for vertebrate limb development Cell 1997, 90:979-990.
5. Niswander L: Limb mutants: what can they tell us about normal limb development? Curr Opin Genet Dev 1997, 7:530-536.
6. Shubin N, Tabin C, Carroll S: Fossils, genes, and evolution of animal limbs. Nature 1997, 388:639-648.
7. Lawrence PA, Struhl G: Morphogens, compartments, and pattern: lessons from Drosophila? Cell 1996, 85:951-961.
8. Cohn MJ, Patel K, Krumlauf R, Wilkinson DG, Clarke JDW, Tickle C: Hox9 genes and vertebrate limb specification. Nature 1997, 387:97-101. An important study following up on the ability of fibroblast growth factors to induce a supernumerary limb. The authors provide strong experimental support for the view that the positioning and type of limb formed is determined by the axial anterior-posterior alignment of Hox gene expression boundaries in the lateral plate mesoderm.
9. Basler K, Struhl G: Compartment boundaries and the control of Drosophila limb pattern by hedgehog protein. Nature 1994, 368:208-214.
10. Heslip TR, Theisen H, Marsh JL: SHAGGY and DISHEVELLED exert opposite effects on wingless and decapentaplagic expression and on positional identity in imaginal discs. Development 1997, 124:1069-1078.
11. ••,13,14•,15], make it clear that distinct dorsal and ventral cell fates in the leg are maintained by mutual repression of these genes.
12. ••], provides the most complete analysis.
13. Morimura S, Maves L, Chen Y, Hoffmann FM: decapentaplegic overexpression affects Drosophila wing and leg imaginal disc development and wingless expression. Dev Biol 1996, 177:136-151.
14. Penton A, Hoffmann FM: Decapentaplegic restricts the domain of wingless during Drosophila limb patterning. Nature 1996, 382:162-164. A detailed study describing the negative effect that Decapentaplegic (Dpp) signaling has on the ability of Hedgehog signaling to induce wingless (wg) expression, on the basis of analysis of clones of cells mutant for the Dpp receptors. Punt and Thick veins. They note that this mechanism operates within the wing as well as the leg, and that within the leg Dpp activity is needed to repress wg expression only in distal, and not in proximal, regions.
15. Johnston LA, Schubiger G: Ectopic expression of wingless in imaginai discs interferes with decapentaplegic expression and alters cell determination. Development 1996, 122:3519-3529.
16. Cohen B, Simcox AA, Cohen SM: Allocation of the thoracic imaginai disc primordia in the Drosophila embryo. Development 1993, 117:597-608.
17. Couso JP, Bate M, Martinez Arias A: A wingless-dependent polar coordinate system in the imaginai discs of Drosophila. Science 1993, 259:484-489.
18. Lecuit T, Cohen SM: Proximal-distal axis formation in the Drosophila leg. Nature 1997, 388:139-145. Although it has generally been thought that proximal-distal patterning in the leg would be regulated only indirectly by wingless (wg) and decapentaplegic (dpp), via the induction of an organizing activity in the center of the disc, these authors show that dpp and wg can have direct effects on proximal-distal patterning.
19. Ng M, Diaz Benjumea FJ, Vincent J-P, Wu J, Cohen SM: Specification of the wing primordium in Drosophila. Nature 1996, 381:316-318. The authors studied early wing development using molecular markers of wing cell fate, such as nubbin, in wingless (wg) mutants and animals with ectopic wg expression. Their analysis demonstrates that wg plays an essential role in defining the region of the disc that is fated to become wing.
20. Diaz-Benjumea FJ, Cohen SM: Interaction between dorsal and ventral cells in the imaginal disc directs wing development in Drosophila. Cell 1993, 75:741-752.
21. Blair SS, Brower DL, Thomas JB, Zavortink M: The role of apterous in the control of dorsoventral compartmentalization and PS integrin gene expression in the developing wing of Drosophila. Development 1994, 120:1805-1815.
22. Cohen B, McGuffin ME, Rfeifle C, Segal D, Cohen SM: apterous, a gene required for imaginai disc development in Drosophila encodes a member of the LIM family of developmental regulatory proteins. Genes Dev 1992, 6:715-729.
23. Speicher SA, Thomas U, Hinz U, Knust E: The Serrate locus of Drosophila and its role in morphogenesis of the wing imaginai discs: control of cell proliferation. Development 1994, 120:535-544.
24. MacCabe JA, Errick J, Saunders JW: Ectodermal control of dorsoventral axis in the leg bud of the chick embryo. Dev Biol 1974, 39:69-82.
25. Michaud JL, Lapointe F, Douarin NM: The dorsoventral polarity of the presumptive limb is determined by signals produced by the somites and by the lateral somatopleure. Development 1997, 124:1453-1463. An elegant study that uses chick-quail chimeras to create a fate map for the prospective limb. One surprising finding is the delineation of the prospective apical ectodermal ridge (AER) to a region of approximately 150μm overlying the entire prospective limb mesoderm. The authors also conducted grafting experiments, which suggest that there are antagonistic axial signals responsible for dorsal-ventral (D-V) specification of the limb ectoderm. The ability of the dorsalizing signal to create a bidorsal limb without disrupting the AER suggests that the timing of D-V specification within the ectoderm may differ from the timing of the D-V signaling that establishes the organizer.
26. ··]).
27. Diaz-Benjumea FJ, Cohen SM: Serrate signals through Notch to establish a Wingless-dependent organizer at the dorsal/ventral compartment boundary of the Drosophila wing. Development 1995, 121:4215-4225.
28. ··], that activation of the Notch pathway can induce the expression of Serrate and Delta, They also describe the requirement for Cut to inhibit Serrate and Delta expression along the dorsal-ventral border. This fact, together with the autonomous inhibition of Notch signaling exerted by these ligands, which the authors describe, leads to an explanation for how Cut maintains Wg expression.
29. Kim J, Sebring A, Esch JJ, Kraus ME, Vorwerk K, Magee J, Carroll SB: Integration of positional signals and regulation of wing formation and identity by Drosophila vestigial gene. Nature 1996, 382:133-138, The authors demonstrate that vestigial is specifically required for cell proliferation in the wing, and further show that ectopic vestigial expression can induce the formation of overgrowths of wing tissue in other imaginal discs. They also expand on their previous analysis of vestigial regulation, and demonstrate that the vestigial boundary enhancer, which directs expression along the dorsal-ventral (D-V) compartment border, is directly regulated by Notch signaling (via Suppressor of Hairless), and that vestigial expression in the rest of the wing is regulated by a quadrant enhancer that responds to both D-V and anterior-posterior compartment boundary signals.
30. ··], also shows that Serrate and Delta positively regulate each other's expression in the wing disc.
31. ··], provide a clear demonstration that Delta plays a role in Notch activation at the dorsal-ventral border. The authors' study of hypomorphic Notch mutant clones suggests that the requirements for Notch activity are different between dorsal and ventral cells.
32. Couso JP, Knust E, Martinez Arias A: Serrate and wingless cooperate to induce vestigial gene expression and wing formation in Drosophila. Curr Biol 1995, 5:1437-1446.
33. Jönsson F, Knust E: Distinct functions of the Drosophila genes Serrate and Delta revealed by ectopic expression during wing development. Dev Genes Evol 1996, 206:91-101. This study of the effects of ectopic expression of Serrate and Delta in the wing disc includes the demonstration that ectopic expression of wingless cannot rescue wing growth in Serrate mutants. These authors also report a more robust reponse to ectopic Delta expression in ventral cells than observed by other investigators; we suggest these differences may be due to variations in the levels of ectopic Delta.
34. Kim J, Irvine KD, Carroll SB: Cell recognition, signal induction, and symmetrical gene activation at the dorsal-ventral boundary of the developing Drosophila wing. Cell 1995, 62:795-802.
35. Irvine KD, Wieschaus E: fringe, a boundary-specific signaling molecule, mediates interactions between dorsal and ventral cells during Drosophila wing development. Cell 1994, 79:595 606.
36. Yuan YP, Schultz J, Mlodzik M, Bork P: Secreted Fringe-like signaling molecules may be glycosyltransferases. Cell 1997, 86:9-11.
37. ··]). They also report that Fringe can inhibit the ability of Ser to influence neurogenesis in the embryo, demonstrating that the ability of Fringe to affect Ser is not restricted to the wing. By swapping the amino terminus (including the presumptive receptor-binding region) of Ser with that of Delta, they localize the sensitivity of Ser→Notch signaling to regulation by Fringe of interactions involving this domain.
38. ··]).
39. Cohn M, Tickle C: Limbs: a model for pattern formation within the vertebrate body plan. Trends Genet 1996, 12:253-257.
40. Grieshammer U, Minowada G, Pisenti JM, Abbott UK, Martin GR: The chick limbless mutation causes abnormalities in limb bud dorsal-ventral patterning: implications for the mechanism of apical ridge formation. Development 1996, 122:3851-3861. One of a cohort of insightful papers that report an analysis of the chick limbless mutant. The authors provide a mechanistic and molecular framework with which to view the patterning signals early in limb bud initiation and the importance of the dorsal-ventral (D-V) boundary for the formation of the apical ectodermal ridge (AER). Anterior-posterior axial information, as studied by Hox gene expression, is present in the prelimb bud, and subsequently becomes dependent on the AER and Sonic hedgehog for its maintenance. The rescue of limbless limb buds by fibroblast growth factor-8 (FGF-8) provides additional support for FGF-8 as the D-V organizing activity.
41. Tanaka M, Tamura K, Ide H: Induction of additional limb at the dorsal-ventral boundary of a chick embryo. Dev Biol 1997, 182:191-203. Grafts of prospective dorsal to ventral or ventral to dorsal limb tissue in quail-chick chimeric embryos highlight the importance of a dorsal-ventral (D-V) ectodermal boundary in the formation of D-V organizing activity.
42. ·]), or a requirement for additional competence-inducing factors to establish the AER. An evolutionarily conserved role for R-Fng in the Notch pathway is suggested by the expression of Notch1 and Serrate2 in the AER, and by the expression of Lunatic Fringe relative to Notch ligands in the chick central nervous system (see also [46,47]).
43. ··] for detailed comments) that describes the expression of the Radical fringe (R-Fng) gene in the chick limb and demonstrates the ability of ectopic R-Fng to influence AER formation.
44. ··] for detailed comments.
45. ··] for detailed comments.
46. Johnston SH, Rauskolb C, Wilson R, Prabhakaran B, Irvine KD, Vogt TF: A family of mammalian Fringe genes implicated in boundary determination and the Notch pathway. Development 1997, 124:2245-2254.
47. Cohen B, Bashirullah A, Dagnino L, Campbell C, Fisher WW, Leow CC, Whiting E, Ryan D, Zinyk D, Boulianne G et al.: Fringe boundaries coincide with Notch-dependent patterning centres in mammals and alter Notch-dependent development in Drosophila. Nat Genet 1997, 16:283-288.
48. Blaumueller CM, Artavanis-Tsakonas S: Comparative aspects of Notch signaling in lower and higher eukaryotes. Perspect Dev Neurobiol 1997, 4:325-343.
49. Shawber C, Boulter J, Lindsell CE, Weinmaster G: Jagged2: a Serrate-like gene expressed during rat embryogenesis. Dev Biol 1996, 180:370-376.
50. Hayashi H, Mochii M, Kodama R, Hamada Y, Mizuno N, Eguchi G, Tachi C: Isolation of a novel chick homolog of Serrate and its coexpression with C-Notch in chick development. Int J Dev Biol 1996, 40:1089-1096.
51. Conton RA, Reaume AG, Rossant J: Notch1 is required for the coordinate segmentation of somites. Development 1995, 121:1533-1545.
52. Swiatek PJ, Lindsell CE, del Amo FF, Weinmaster G, Gridley T: Notch1 is essential for postimplantation development in mice. Genes Dev 1994, 8:707-719.
53. Sidow A, Bulotsky MS, Kerrebrock AW, Bronson RT, Daly MJ, Reeve MP, Hawkins TL, Birren BW, Jaenisch R, Lander ES: Serrate2 is disrupted in the mouse limb development mutant syndactylism. Nature 1997, 389:722-725. Positional cloning of the mouse syndactylism mutant as an allele of Serrate2 reveals a functional requirement for Notch ligands in proper apical ectodermat ridge formation.
54. Loomis CA, Harris E, Michaud J, Wurst W, Hanks M, Joyner AL: The mouse Engrailed-1 gene and ventral limb patterning, Nature 1996, 382:360-363. Describes the creation of a gene-targeted mutation of mouse Engrailed-1. These authors demonstrate that Engrailed-1 is essential for dorsal-ventral specification of distal limb structures and proper formation of the apical ectodermal ridge.
55. ··] and Rodriguez-Esteban et al., 1997. [43··]).
56. Rulifson EJ, Blair SS: Notch regulates wingless expression and is not required for reception of the paracrine wingless signal during wing margin neurogenesis in Drosophila. Development 1995, 121:2813-2824.
57. ··], provide a clear and compelling demonstration that Wg acts directly and at long range to regulate target gene expression in Drosophila imaginal discs.
58. Neumann CJ, Cohen SM: Long-range action of Wingless organizes the dorsal-ventral axis of the Drosophila wing. Development 1997, 124:871-880. These authors show, as do Zecca et al., 1996, [57··], that Wingless (Wg) acts directly and at long range to modulate target gene expression in the Drosphila wing, and that three distinct targets are sensitive to different levels of Wg activity. Their analysis employs both mutants for genes involved in Wg signaling and ectopic expression of Wg.
59. D, a dominant allele of the Drosophila gene Serrate. Genetics 1995, 139:203-213.
60. Kooh PJ, Fehon RG, Muskavitch MAT: Implications of dynamic patterns of Delta and Notch expression for cellular interactions during Drosophila development Development 1993, 117:493-507.
61. Neumann CJ, Cohen SM: A hierarchy of cross-regulation involving Notch, wingless, vestigial, and cut organizes the dorsal/ventral axis of the Drosophila wing. Development 1996, 122:3477-3485. Describes an investigation of signaling interactions at the dorsal-ventral wing boundary in which the authors analyzed the regulatory relationship between vestigial and wingless (wg), and the effects of Notch and Wg activity on the expression of cut, wg, and vestigial.
62. Klein T, Brennan K, Matinez Arias A: An intrinsic dominant negative activity of Serrate that is modulated during wing development in Drosophila. Dev Biol 1997, 189:123-134.
63. Williams JA, Paddock SW, Vorwerk K, Carroll SB: Organization of wing formation and induction of a wing-patterning gene at the dorsal/ventral compartment boundary. Nature 1994, 368:299-305.
64. Akita K, Francis-West P, Vargesson N: The ectodermal control in chick limb development: Wnt-7a, Shh, Bmp-2, and Bmp-4 expression and the effect of FGF-4 on gene expression. Mech Dev 1996, 60:127-137.
65. Summerbell D, Lewis JH, Wolpert L: Positional information in chick limb morphogenesis. Nature 1973, 244:492-496.
66. Ohuchi H, Nakagawa T, Yamamoto A, Araga A, Ohata T, Ishimaru Y, Yoshioka H, Kuwana T, Nohno T, Yamasaki M et al.: The mesenchymal factor, FGF10, initiates and maintains the outgrowth of the chick limb bud through interaction with FGFB, an apical ectodermal factor. Development 1997, 124:2235-2244. These authors report important new information about the relationship of individual fibroblast growth factor (FGF) family members to limb bud intiation and apical ectodermal ridge (AER) maintenance. The authors show that localized production of FGF-10 in the lateral plate mesoderm may be the key factor to promote limb bud initation and FGF-8 expression in the limb ectoderm. Evidence for a subsequent reciprocal positive feedback loop between FGF-10 expression in the limb mesoderm and both FGF-B expression in the AER and Sonic hedgehog expression in posterior limb mesoderm is also presented.
67. Chiang C, Litingtung Y, Lee E, Young KE, Corden J, Westphal H, Beachy PA: Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 1996, 383:407-413. Eagerly awaited phenotypic analysis results from the targeted gene disruption of the mouse Sonic hedgehog gene demonstrate a functional requirement for Sonic hedgehog for the proper patterning of many structures, including the limb, and reinforces the suggestion of the postulated coordinated feedback interactions between the limb organizing centers.
68. ··] with respect to cell fate restrictions and the contributions of the ectoderm to the AER.
69. Parr BA, McMahon A: Dorsalizing signal Wnt-7a required for normal polarity fo D-V and A-P axes of mouse limb. Nature 1995, 374:350-353.
70. De Celis JF, Garca-Bellido A: Roles of the Notch gene in Drosophila wing morphogenesis. Mech Dev 1994, 46:109-122.
71. Bhanot P, Brink M, Samos CH, Hsieh J-C, Wang Y, Macke JP, Andrew D, Nathans J, Nusse R: A new member of the frizzled family from Drosophila functions as a Wingless receptor. Nature 1996, 382:225-230.