2 Molecular and Cellular Basis of Pattern Formation during Vertebrate Limb Development

Current Topics in Developmental Biology

Volumn 41, Issue C, 1998, Pages 37-66

  Ng, Jennifer K ^a   Tamura, Koji ^a   Büscher, Dirk ^a   Carlos, Juan ^a   Belmonte, Izpisúa ^a  

^a SALK INSTITUTE FOR BIOLOGICAL STUDIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FIBROBLAST GROWTH FACTOR;

ANIMAL; CHICK EMBRYO; CYTOLOGY; ECTODERM; GENE EXPRESSION REGULATION; GENETICS; HOMEOBOX; LIMB; MESODERM; MORPHOGENESIS; PHYSIOLOGY; PRENATAL DEVELOPMENT; REVIEW; TRANSPLANTATION; VERTEBRATE;

ANIMALS; BODY PATTERNING; CHICK EMBRYO; ECTODERM; EXTREMITIES; FIBROBLAST GROWTH FACTORS; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GENES, HOMEOBOX; MESODERM; VERTEBRATES;

EID: 0032888798     PISSN: 00702153     EISSN: None     Source Type: Book Series    
DOI: 10.1016/S0070-2153(08)60269-0     Document Type: Article

References (146)

1. Anderson, R., Landry, M., Reginelli, A., Taylor, G., Achkar, C., Gudas, L., Muneoka, K., Conversion of anterior limb bud cells to ZPA signaling cells in vitro and in vivo. Dev. Biol. 164 (1994), 1421-1433.
2. Bulfone, A., Kim, H.-J., Puelles, L., Porteus, M.H., Grippo, J.E., Rubenstein, J.L.R., The mouse Dlx-2 (Tes-1) gene is expressed in spatially restricted domains of the fore-brain face and limbs in midgestation mouse embryos. Mechanisms Dev. 40 (1993), 129-140.
3. Büscher, D., Bosse, B., Heymer, J., Ru'ther, U., Evidence for genetic control of Sonic-hedgehog by GIB in mouse limb development. Mechanisms Dev. 62 (1997), 175-182.
4. Cameron, J., Fallen, J.F., Evidence for polarizing zone in the limb buds of Xenopus laevis. Dev. Biol. 55 (1977), 320-330.
5. Carrington, J.L., Fallon, J., Initial limb budding is independent of apical ectodermal ridge activity: Evidence from a limbless mutant. Development 104 (1988), 361-367.
6. Charite, J., de Graaff, W., Shen, S., Deschmaps, J., Ectopic expression of Hoxb-S causes duplication of the ZPA in the forelimb and homeotic transformation of axial structures. Cell 78 (1994), 589-601.
7. Chaube, S., On axiation and symmetry in the transplanted wing of the chick. J. Exp. Zool. 140 (1959), 29-77.
8. Chiang, C., Litingtung, Y., Lee, E., Young, K.E., Corden, J.L., Westphal, H., Beachy, P.A., Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 383 (1996), 407-413.
9. Cohn, M., Izpisúa-Belmonte, J.C., Abud, H., Heath, J.K., Tickle, C., FGF-2 application can induce additional limb formation from the flank of chick embryos. Cell 80 (1994), 739-746.
10. Cohn, M.J., Izpisúa-Belmonte, J.C., Abud, H., Heath, J.K., Tickle, C., Fibroblast growth factors induce additional limb development from the flank of chick embryos. Cell 80 (1995), 739-746.
11. Cohn, M.J., Patel, K., Krumlauf, R., Wilkinson, D.G., Clarke, J.D.W., Tickle, C., Hox9 genes and vertebrate limb specification. Nature 387 (1997), 97-101.
12. Crossley, P.H., Martin, G.R., The mouse Fgf-S gene encodes a family of polypep-tides and is expressed in regions that direct outgrowth and patterning in the developing embryo. Development 121 (1995), 439-451.
13. Crossley, P.H., Minowada, G., MacArthur, C.A., Martin, G.R., Roles for FGF-8 in the induction, initiation and maintenance of chick limb development. Cell 84 (1996), 127-136.
14. Davidson, D.R., Crawley, A., Hill, R.E., Tickle, C., Position-dependent expression of two related homeobox genes in developing vertebrate limbs. Nature 352 (1991), 429-431.
15. Davis, A.P., Capecchi, M.R., A mutational analysis of the 5′HoxD genes: Dissection of genetic interactions during limb development in the mouse. Development 122 (1996), 1175-1185.
16. Davis, A.P., Witte, D.P., Hsieh-Li, H.M., Potter, S.S., Capecchi, M.R., Absence of radius and ulna in mice lacking hoxa-11 and hoxd-11. Nature 375 (1995), 791-795.
17. Dealy, C.N., Roth, A., Ferrari, D., Brown, A., Kosher, R., Wnt-5a and Wnt-7a are expressed in the developing chick limb bud in a manner suggesting roles in pattern formation along the proximodistal and dorsoventral axes. Mechanisms Dev. 43 (1993), 175-186.
18. De Meoriooze, L., Dickson, C., Skeletal disorders associated with fibroblast growth factor mutations. Curr. Opin. Genet. Dev. 7 (1997), 378-385.
19. Deng, C., Bedford, M., Li, M., Xu, X., Yang, X., Dunmore, X.J., Leder, P., Fibroblast growth factor receptor-1 (FGFR-1) is essential for normal neural tube and limb development. Dev. Biol. 185 (1997), 42-54.
20. Dollé, P., Izpisúa-Belmonte, J.-C., Falkenstein, H., Renucci, A., Duboule, D., Coordinate expression of three murine Hox-5 complex homeobox-containing genes during limb pattern formation. Nature 342 (1989), 767-772.
21. Dollé, P., Ruberte, E., Kastner, P., Petkovich, M., Stoner, C.M., Gudas, L.J., Chambon, P., Differential expression of genes encoding a, b, and g retinoic acid receptors and CRABP in the developing limbs of the mouse. Nature 342 (1989), 702-705.
22. Dollé, P., Price, M., Duboule, D., Expression of the murine Dlx-1 homeobox gene during facial, ocular, and limb development. Differentiation 49 (1992), 93-99.
23. Dollé, P., Dierich, A., LeMeur, M., Shimmang, T., Schuhbaur, B., Chambon, P., Duboule, D., Disruption of the Hoxd-13 gene induces localized heterochrony. Cell 75 (1993), 431-441.
24. Dono, R., Zeller, R., Cell-type specific nuclear translocation of fibroblast growth fac-tor-2 isoforms during chicken kidney and limb morphogenesis. Dev. Biol. 163 (1994), 316-330.
25. Duboule, D., Vertebrate Hox genes and proliferation: An alternative pathway to homeosis?. Curr. Opin. Genet. Dev. 5 (1995), 525-528.
26. Duboule, D., Morata, G., Colinearity and functional hierachy among genes of the ho-meotic complexes. Trends Genet. 10 (1994), 358-364.
27. Duprez, D.M., Kostakopoulou, K., Francis-West, P.H., Tickle, C., Brickell, P.M., Activation of Fgf-4 and HoxD gene expression by BMP-2 expressing cells in the developing chick limb. Development 122 (1996), 1821-1828.
28. Fallon, J.F., Crosby, G.M., Polarizing zone activity in limb buds of amniotes. Ede, D.A., Hinchliffe, J.R., Balls, M., (eds.) ”Vertebrate Limb and Somite Morphogenesis“, 1977, Cambridge University Press, Cambridge, UK., 55-71.
29. Fallon, J., López, A., Ros, M., Savage, M., Olwin, B., Simandl, B., FGF-2: Apical ec-todermal ridge growth signal for chick limb development. Science 264 (1994), 104-107.
30. Favier, B., LeMeur, M., Chambon, P., Dolle, P., Axial skeleton homeosis and forelimb malformations in Hoxd-11 mutant mice. Proc. Natl. Acad. Sci. USA 92 (1995), 310-314.
31. Fernandez-Teran, M., Piedra, M.E., Simandl, B.K., Fallon, J.F., Ros, M.A., Limb initiation and development is normal in the absence of mesonephros. Dev. Biol 189 (1997), 246-255.
32. Ferrari, D., Sumoy, L., Gannon, J., Sun, H., Brown, A.M., Upholt, W.B., Kosher, R.A., The expression of the distal-less homeobox-containing gene Dlx-5 in the developing chick limb bud suggests its involvement in apical ectodermal ridge activity, pattern formation, and cartilage differentiation. Mechanisms Dev. 52 (1995), 257-264.
33. Francis, P.H., Richardson, M.K., Brickell, P.M., Tickle, C., Bone morphogenetic proteins and a signaling pathway that controls patterning in the developing chick limb. Development 120 (1994), 209-218.
34. Francis-West, P.H., Robertson, K.E., Ede, D.A., Rodriguez, C., Izpisúa-Belmonte, J.C., Houston, B., Burt, D., Gribben, C., Brickell, P., Tickle, C., Expression of genes encoding bone morphogenetic proteins and sonic hedgehog in talpid (ta3) limb buds: Their relationships in the signaling cascade involved in limb patterning. Dev. Dynam. 203 (1995), 187-197.
35. Fromental-Ramain, C., Warot, X., Messadecq, N., LeMeur, M., Dolle, P., Chambon, P., Hoxa-13 and Hoxd-13 play a crucial role in the patterning of the limb autopod. Development 122 (1996), 2997-3011.
36. Gañan, Y., Macias, D., Duterque-Coquillaud, M., Ros, M., Hurle, J.M., Role of TGF-βs and BMPs as signals controlling the position of the digits and the areas of cell death in the developing chick limb autopod. Development 122 (1996), 2349-2357.
37. Geduspan, G.S., MacCabe, J.A., Transfer of information from mesoderm to ectoderm at the onset of limb development. Anat. Kec. 224 (1989), 79-87.
38. Geduspan, J.S., Solursh, M., A growth promoting influence from the mesonephros during limb outgrowth. Dev. Biol. 151 (1992), 242-250.
39. Gibson-Brown, J.J., Agulnik, S.I., Silver, L.M., Niswander, L., Papaioannou, V.E., Involvement of T-boxs genes Tbx2-Tbx5 in vertebrate limb specification and development. Development 125 (1998), 2499-2509.
40. Globus, M., Vethamany-Globus, S., An in vitro analogue of early chick limb bud outgrowth. Differentiation 6 (1976), 91-96.
41. Goff, D.J., Tabin, C.J., Analysis of Hoxd-13 and Hoxd-11 misexpression in chick limb buds reveals that Hox genes affect both bone condensation and growth. Development 124 (1997), 627-636.
42. Grieshammer, U., Minowada, G., Pisenti, J.M., Abbott, U.K., Martin, G.A., The chick limbless mutation causes abnormalities in limb bud dorsal-ventral patterning: Implications for the mechanism of apical ridge formation. Development 122 (1996), 3851-3861.
43. Hamburger, V., Hamilton, H., A series of normal stages in the development of the chick embryo. J. Morphol. 88 (1951), 49-92.
44. Haramis, A.G., Brown, J.M., Zeller, R., The limb deformity mutation disrupts the SHH/FGF-4 feedback loop and regulation of 5′HoxD genes during limb pattern formation. Development 122 (1995), 4237-4245.
45. Hardy, A., Richardson, M.K., Francis-West, P.H., Rodriguez, C., Izpisua-Belmonte, J.C., Wolpert, L., Gene expression, polarizing activity and skeletal patterning in reaggregated hind limb mesenchyme. Development 121 (1995), 4329-4337.
46. Heikinheimo, M., Lawshe, A., Shackleford, G.M., Wilson, D.B., MacArthur, C.A., Fgf-& expression in the postgastrulation mouse suggests roles in the development of the face, limbs and central nervous system. Mechanisms Dev. 48 (1994), 129-138.
47. Helms, J.A., Kim, C.H., Eichele, G., Thaller, C., Retinoic acid signaling is required during early chick limb development. Development 122 (1996), 1385-1394.
48. Hogan, B.L.M., Bone morhogenetic proteins in development. Curr. Opin. Genet. Dev. 6 (1996), 432-438.
49. Ide, H., Wada, N., Uchiyama, K., Sorting out of cells from different parts and stages of the chick limb bud. Dev. Biol. 162 (1994), 71-76.
50. Isaac, A., Rodrigues-Esteban, C., Ryan, A., Altabef, M., Tsukui, T., Patel, K., Tickle, C., Izpisúa-Belmonte, J.C., Tbx genes and limb identity in chick embryo development. Development 125 (1998), 1867-1875.
51. Izpisúa-Belmonte, J.C., Falkenstein, H., Dolle, P., Renucci, A., Duboule, D., Murine genes related to the Drosophila AdbB homeotic gene are sequentially expressed during development of the posterior part of the body. EMBO 10 (1991), 2279-2289.
52. Izpisúa-Belmonte, J.C., Tickle, C., Dolle, P., Wolpert, L., Duboule, D., Expression of the homeobox Hox-4 genes and the specification of position in chick wing development. Nature 350 (1991), 585-589.
53. Izpisúa-Belmonte, J.C., Brown, J.M., Duboule, D., Tickle, C., Expression of Hox-4 genes in the chick wing links pattern formation to the epithelial—mesenchymal interactions that mediate growth. EMBO J. 11 (1992), 1451-1457.
54. Jones, F.S., Prediger, E.A., Bittner, D.A., DeRobertis, E.M., Edelman, G.M., Cell adhesion molecules as targets for Hox genes: Neural cell adhesion molecule promoter activity is modulated by cotransfection with Hox-2.5 and -2.4. Proc. Natl. Acad. Sci. USA 89 (1992), 2086-2090.
55. Kengaku, M., Capdevila, J., Rodriguez-Esteban, C., De La Pena, J., Johnson, R.L., Izpisua-Belmonte, J.C., Tabin, C., Distinct WNT pathways regulating AER formation and dorsoventral polarity in the chick limb bud. Science 280 (1998), 1274-1277.
56. Kieny, M., Variation in the inductive capacity of mesoderm and the competence of ectoderm during primary induction in the chick limb bud. Arch. Anat. Microsc. Morphol. Exp. 57 (1968), 401-418.
57. Kostakopoulou, K., Vogel, A., Brickell, P., Tickle, C., ”Regeneration“ of wing bud stumps of chick embryos and reactivation of Msx-1 and Shh expression in response to FGF-4 and ridge signals. Mechanisms Dev. 55 (1996), 119-131.
58. Kuhlman, J., Niswander, L., Limb deformity proteins: role in mesenchymal induction of the apical ectodermal ridge. Development 124 (1997), 133-139.
59. Laufer, E., Nelson, C.E., Johnson, R.L., Morgan, B.A., Tabin, C., Sonic hedgehog and Fgf-4 act through a signaling cascade and feedback loop to integrate growth and patterning of the developing limb bud. Cell 79 (1994), 993-1003.
60. Laufer, E., Dahn, R., Orozco, O.E., Yeo, C.-Y., Pisenti, J., Abbott, U.K., Fallon, J.F., Tabin, C., The radical fringe expression boundary in the limb bud ectoderm regulates AER formation. Nature 386 (1997), 366-373.
61. Logan, C., Hornbruch, A., Campbell, I., Lumsden, A., The role of Engrailed in establishing the dorsoventral axis of the chick limb. Development 124 (1997), 2317-2324.
62. Loomis, C.A., Harris, E., Michaud, J., Wurst, W., Hanks, M., Joyner, A.L., The En-grailed-l gene and ventral limb patterning. Nature 382 (1996), 360-363.
63. Lopez-Martinez, A., Chang, D.T., Chiang, C., Porter, J.A., Ros, M.A., Simandl, B.K., Beachy, P.A., Fallon, J.F., Limb-patterning activity and restricted posterior localization of the amino-terminal product of sonic hedgehog cleavage. Curr. Biol. 5 (1995), 791-796.
64. Lu, H.C., Revelli, J.P., Goering, L., Thaller, C., Eichele, G., Retinoid signaling is required for the establishment of ZPA and for the expression of Hoxb-8, a mediator of ZPA formation. Development 124 (1997), 1643-1651.
65. MacCabe, J.A., Errick, J.E., Saunders, J.W.J., Ectodermal control of the dorsoventral axis in the leg bud of the chick embryo. Dev. Biol. 39 (1974), 69-82.
66. Macias, D., Ganan, Y., Sampath, T.K., Piedra, M.E., Ros, M.A., Hurle, J.M., Role of BMP-2 and OP-1 (BMP-7) in programmed cell death and skeletogenesis during chick limb development. Development 124 (1997), 1109-1117.
67. Mahmood, R., Bresnick, J., Hornbruch, A., Mahony, C., Morton, N., Colquhoun, K., Martin, P., Lumsden, A., Dickson, C., Mason, I., A role for FGF-8 in the initiation and maintenance of vertebrate limb bud outgrowth. Curr. Biol. 5 (1995), 797-806.
68. Marigo, V., Johnson, R.L., Vortkamp, A., Tabin, C.J., Sonic hedgehog differentially regulates expression of GLI and G/,/3 during limb development. Dev. Biol. 180 (1996), 273-283.
69. Marti, E., Takada, R., Bumcrot, D.A., Sasaki, H., McMahon, A.P., Distribution of sonic hedgehog peptides in the developing chick and mouse embryo. Development 121 (1995), 2537-2547.
70. Martin, G.R., The roles of FGFs in the early development of vertebrate limbs. Genes & Dev. 12 (1998), 1571-1586.
71. Masuya, H., Sagai, T., Wakana, S., Moriwaki, K., Shiroishi, T., A duplicated zone of polarizing activity in polydactylous mouse mutants. Genes Dev. 9 (1995), 1645-1653.
72. Masuya, H., Sagai, T., Moriwaki, K., Shiroshi, T., Multigenic control of the localization of the zone of polarizing activity in limb morphogenesis in the mouse. Dev. Biol. 182 (1997), 42-51.
73. McGinnis, W., Krumlauf, R., Homeobox genes and axial patterning. Cell 68 (1992), 283-302.
74. Michaud, J.L., Lapointe, F., Le Douarin, N.M., The dorsoventral polarity of the presumptive limb is determined by signals produced by the somites and by the lateral so-matopleure. Development 124 (1997), 1453-1463.
75. Moon, R.T., Brown, J.D., Torres, M., WNTs modulate cell fate and behavior during vertebrate development. Trends Genet. 13 (1997), 157-162.
76. Morgan, B.A., Izpisúa-Belmonte, J.-C., Duboule, D., Tabin, C.J., Targeted misex-pression of Hox-4.6 in the avian limb bud causes apparent homeotic transformations. Nature 358 (1992), 236-239.
77. Muragaki, Y., Mundlos, S., Upton, J., Olsen, B.R., Altered growth and branching patterns in synpolydactyly caused by mutations in HOXD13. Science 272 (1996), 548-551.
78. Nelson, C.E., Morgan, B.A., Burke, A.C., Laufer, E., DiMambro, E., Murtaugh, L.C., Gonzales, E., Tessarollo, L., Parada, L.E., Tabin, C., Analysis of hox gene expression in the chick limb bud. Development 122 (1996), 1449-1466.
79. Neubüser, A., Koseki, H., Balling, R., Characterization and developmental expression of Pajc9, a paired-box-containing gene related to Pax}. Dev. Biol. 170 (1995), 701-716.
80. Niswander, L., Martin, G.R., FGF-4 expression during gastrulation, myogenesis, limb and tooth development in the mouse. Development 114 (1992), 755-768.
81. Niswander, L., Martin, G.R., FGF-4 and BMP-2 have opposite effects on limb growth. Nature 361 (1994), 68-71.
82. Niswander, L., Tickle, C., Vogel, A., Booth, I., Martin, G.R., FGF-4 replaces the apical ectodermal ridge and directs outgrowth and patterning of the limb. Cell 75 (1993), 579-587.
83. Niswander, L., Jeffrey, S., Martin, G.R., Tickle, C., A positive feedback loop coordinates growth and patterning in the vertebrate limb. Nature 371 (1994), 609-612.
84. Nohno, T., Noji, S., Koyama, E., Ohyama, K., Myokai, F., Involvement of the Chox-4 chicken homeobox genes in determination of anteroposterior axial polarity during limb development. Cell 64 (1991), 1197-1205.
85. Noji, S., Nohno, T., Koyama, E., Muto, K., Ohyama, K., Yoshinobu, A., Tamura, K., Oshugi, K., Ide, H.J., Taniguchi, S., Saito, T., Retinoic acid induces polarizing activity but is unlikely to be a morphogen in the chick limb bud. Nature 350 (1991), 83-86.
86. Noramly, S., Pisenti, J., Abbott, U., Morgan, B., Gene expression in the limbless mutant: Polarized gene expression in the absence of Shh and an AER. Dev. Biol. 179 (1996), 339-346.
87. Nusse, R., A versatile transcriptional effector of Wingless signaling. Cell 89 (1997), 321-323.
88. Nusse, R., Varmus, H.E., Wnt genes. Cell 69 (1992), 1073-1087.
89. Ogura, T., Alvarez, I.S., Vogel, A., Rodriguez, C., Evans, R.M., Izpisua-Belmonte, J.C., Evidence that Shh cooperates with a retinoic acid inducible cofactor to establish ZPA-like activity. Development 122 (1996), 537-542.
90. Ohuchi, H., Nakagawa, T., Yamamoto, A., Araga, A., Ohata, T., Ishimaru, Y., Yoshioka, H., Kuwana, T., Nohono, T., Yamasaki, M., Itoh, N., Noji, S., The mesenchymal factor, FGF-10, initiates and maintains the outgrowth of the chick limb bud through interaction with FGF-8, an apical ectodermal factor. Development 124 (1997), 2235-2244.
91. Ohuchi, H., Takeuchi, J., Yoshioka, H., Ishimaru, Y., Ogura, K., Noji, S., Correlation of wing-leg identity in ectopic FGF-induced chimeric limbs with the differential expression of chick Tbx5 and Tbx4. Development 125 (1998), 51-60.
92. Parr, B.A., McMahon, A.P., Dorsalizing signal Wnt-la required for normal polarity of DV and AP axes of mouse limb. Nature 374 (1995), 350-353.
93. Pautou, M.P., Establissement de 1′axe dorsoventral dans the pied de I'embryon de poulet. J. Embryol. Exp. Morphol. 42 (1977), 177-194.
94. Pautou, M.P., Kieny, M., Interaction ectomesodermique dans 1′estlissement de la po-larite dorsoventrale du pied de I'embryon de poulet. J. Embryol. Exp. Morphol. 11 (1973), 765-789.
95. Prahlad, R.B., Skala, G., Jones, D.B., Briles, W.S., Limbless: A new genetic variant mutant in the chick. J. Exp. Zool. 209 (1979), 427-434.
96. Riddle, R.D., Randy, L.J., Laufer, E., Tabin, C., Sonic hedgehog mediates the polarizing activity of the ZPA. Cell 75 (1993), 1401-1416.
97. Riddle, R.D., Ensini, M., Nelson, C., Tsuchida, T., Jessell, T., Tabin, C., Induction of the LIM homeobox gene Lmx-l by Wnt-la establishes dorsoventral pattern in the vertebrate limb. Cell 83 (1995), 631-640.
98. Rodriguez, C., Kos, R., Macias, D., Abbott, K., Izpisua-Belmonte, J.C., Shh, HoxD, Bmp-2, and Fgf-4 gene expression during development of the polydactylous talpid2, dip-lopodial, and diplopodia4 mutant chick limb buds. Dev. Genet. 19 (1996), 26-32.
99. Rodriguez-Esteban, C., Schwabe, J.W.R., De La Pena, J., Foys, B., Eshelman, B., Izpisua-Belmonte, J.C., Radical fringe positions the AER at the dorsoventral boundary of the vertebrate limb and induces elaboration of the proximodistal axis. Nature 386 (1997), 360-366.
100. C. Rodriguez-Esteban, J. W. R. Schwabe, and J. De La Pena, D. E. Rincon-Limas, J. Botas, J. C. Izpisua-Belmonte, (1997b). Lhx2, a vertebrate homolgue of apterous, regulates fringe expression and outgrowth during vertebrate limb development. Submitted for publication.
101. Ros, M.A., Lopez-Martinez, A., Simandl, B.K., Rodriguez, C., Izpisua-Belmonte, J.C., Dahn, R., Fallen, J., The limb field mesoderm determines initial limb bud anteroposterior asymmetry and budding independent of sonic hedgehog or apical ectodermal gene expressions. Development 122 (1996), 2319-2330.
102. Rosen, V., Thies, R.S., The BMP proteins in bone formation and repair. Trends Genet. 8 (1992), 97-102.
103. Saunders, J.W.J., The proximodistal sequence of the origin of the parts of the chick wing and the role of the ectoderm. J. Exp. Zool. 108 (1948), 363-404.
104. Saunders, J.W.J., Developmental control of three-dimensional polarity in the avian limb. Ann. N.Y. Acad. Sci. 193 (1972), 29-42.
105. Saunders, J.W., Gasseling, M.T., Ectodermal-mesenchymal interactions in the origin of wing symmetry. Fleischmajer, R., Bil-lingham, R.E., (eds.) ”Epithelial-Mesenchymal Interactions“, 1968, Williams and Wilkins, Baltimore, MD., 78-97.
106. Saunders, J.W.J., Reuss, C., Inductive and axial properties of prospective wing-bud mesoderm in the chick embryo. Dev. Biol. 38 (1974), 41-50.
107. Savage, M.P., Hart, C.E., Riley, B.B., Sasse, J., Olwin, B.B., Fallen, J.F., Distribution of FGF-2 suggests it has a role in chick limb bud growth. Dev. Dynam. 198 (1993), 159-170.
108. Searls, R.L., Janners, M.Y., The initiation of limb bud outgrowth in the embryonic chick. Dev. Biol. 24 (1971), 198-213.
109. Simeone, A., Acampora, D., Pannese, M., D'Esposito, M., Stornaiuolo, A., Gulisano, M., Mal-lamaci, A., Kastury, K., Druck, T., Huebner, K., Boncinelli, E., Cloning and characterization of two members of the vertebrate Dlx gene family. Proc. Natl. Acad. Sci. USA 91 (1994), 2250-2254.
110. Small, K.M., Potter, S.S., Homeotic transformation and limb defects in HoxA11 mutant mice. Genes Dev. 7 (1993), 2318-2328.
111. Stephens, T.D., McNulty, T.R., Evidence for a metameric pattern in the development of the chick humerus. J. Embryol. Exp. Morphol. 61 (1981), 191-205.
112. Stephens, T.D., Beier, R.L., Bringhurst, D.C., Hiatt, S.R., Prestridge, M., Pugmire, D.E., Willis, H.J., Limbless in the early chick embryo lateral plate. Dev. Biol. 133 (1989), 1-7.
113. Strecker, T.R., Stephens, T.D., Peripheral nerves do not play a trophic role in limb skeletal morphogenesis. Teratology 27 (1983), 159-167.
114. Summerbell, D., The effects of local application of retinoic acid to the anterior margin of the developing chick limb. J. Embryol. Exp. Morphol. 78 (1983), 269-289.
115. Suzuki, H.R., Sakamoto, H., Yoshida, T., Sugimura, T., Terada, M., Solursh, M., Localization of Hst1 transcripts to the apical ectodermal ridge in the mouse embryo. Dev. Biol. 150 (1992), 219-222.
116. Tamura, K., Aoki, Y., Ide, H., Induction of polarizing activity by retinoic acid occurs independently of duplicate formation in developing chick limb buds. Dev. Biol. 158 (1993), 341-349.
117. Tanaka, M., Tamura, K., Noji, S., Nohno, T., Ide, H., Induction of additional limb at the dorsal-ventral boundary of a chick embryo. Dev. Biol. 182 (1997), 191-203.
118. Thaller, C., Eichele, G., Identification and spatial distribution of retinoids in the developing chick limb bud. Nature 327 (1987), 625-628.
119. Thomsen, G.H., Antagonism within and around the organizer: BMP inhibitors in vertebrate body patterning. Trend Genet. 13 (1997), 209-211.
120. Tickle, C., Retinoic acid and chick limb bud development. Development Suppl. 1 (1991), 113-121.
121. Tickle, C., Vertebrate limb development. Curr. Biol. 5 (1995), 478-484.
122. Tickle, C., Eichele, G., Vertebrate limb development. Annu. Rev. Cell Biol. 10 (1994), 121-152.
123. Tickle, C., Summerbell, D., Wolpert, L., Positional signaling and specification of digits in chick limb morphogenesis. Nature 254 (1975), 199-202.
124. Tickle, C., Alberts, B., Wolpert, L., Lee, J., Local application of retinoic acid to the limb bud mimics the action of the polarizing region. Nature 296 (1982), 554-566.
125. Tickle, C., Lee, J., Eichele, G., A quantitative analysis of the effect of all-trans-retinoic acid on the pattern of chick wing development. Dev. Biol. 109 (1985), 82-95.
126. Tickle, C., Retinoic acid and chick limb bud development. Development Suppl. 1 (1991), 113-121.
127. Todt, W., Fallen, J.F., Development of the apical ectodermal ridge in the chick wing bud. J. Embryol. Exp. Morphol. 80 (1984), 21-41.
128. Vogel, A., Rodriguez, C., Warnken, W., Izpisúa-Belmonte, J.C., Dorsal cell fate specified by chick Lmx1 during vertebrate limb development. Nature 378 (1995), 716-720.
129. Vogel, A., Rodriguez, C., Izpisúa-Belmonte, J.C., Involvement of FGF-8 in initiation, outgrowth and patterning of the vertebrate limb. Development 122 (1996), 1737-1750.
130. Vortkamp, A., Lee, K., Lanske, B., Segre, G.V., Kronenberg, H.M., Tabin, C.J., Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein. Science 273 (1996), 613-622.
131. Wanek, N., Gardiner, D.M., Muneoka, K., Bryant, S.V., Conversion by retinoic acid of anterior cells into ZPA cells in the chick wing bud. Nature 350 (1991), 81-83.
132. Watanabe, Y., Le Dourain, N.M., A role for BMP-4 in the development of subcutaneous cartilage. Mechanisms Dev. 57 (1996), 69-78.
133. Waters, N.F., Bywaters, J.H., A lethal embryonic wing mutation in domestic fowl. J. Hered. 34 (1943), 213-217.
134. Wolpert, L., Positional information and pattern formation. Curr. Top. Dev. Biol. 6 (1971), 183-224.
135. Wurst, W., Auerbach, A.B., Joyner, A.L., Multiple developmental defects in En- grailed-l mutant mice: An early mid-hindbrain deletion and patterning defects in forelimbs and sternum. Development 120 (1994), 2065-2075.
136. Yamaguchi, T., Rossant, J., Fibroblast growth factors in mammalian development. Curr. Opin. Genet. Dev. 5 (1995), 485-491.
137. Yang, Y., Niswander, L., Interaction between the signaling molecules WNT-7a and SHH during vertebrate limb development: Dorsal signals regulate anteroposterior patterning. Cell 80 (1995), 939-947.
138. Yokouchi, Y., Sasaki, H., Kuroiwa, A., Homeobox gene expression correlated with the bifurcation process of limb cartilage development. Nature 353 (1991), 443-445.
139. Yokouchi, Y., Nakazato, S., Yamamoto, M., Goto, Y., Kameda, T., Iba, H., Kuroiwa, A., Misexpression of Hoxa-13 induces cartilage homeotic transformation and changes cell adhesiveness in chick limb buds. Genes Dev. 9 (1995), 2509-2522.
140. Yokouchi, Y., Sakiyama, J., Kameda, H., Iba, A., Suzuki, A., Ueno, N., Kuroiwa, A., BMP-2/-4 mediate programmed cell death in chicken limb bud. Development 122 (1996), 3725-3734.
141. Zakany, J., Duboule, D., Correlation of expression of Wnt-l in developing limbs with abnormalities in growth and skeletal patterning. Nature 36 (1993), 546-549.
142. Zeller, R., Duboule, D., Dorsoventral limb polarity and origin of the ridge: On the fringe of independence?. BioEssays 19 (1997), 541-546.
143. Zeller, R., Jackson-Grusby, L., Leder, P., The limb deformity gene is required for apical ectodermal ridge differentiation and anteroposterior limb pattern formation. Genes Dev. 3 (1989), 1481-1492.
144. Zhang, H., Hu, G., Wang, H., Sciavolino, P., Her, N., Shen, M.M., Abate-Shen, C., Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism. Mol. Cell. Biol. 17 (1997), 2920-2932.
145. Zou, H., Niswander, L., Requirement for BMP signaling in interdigital apoptosis and scale formation. Science 272 (1996), 738-741.
146. Zwilling, E., Interaction between limb bud ectoderm in the chick embryo. IV. Experiments with a wingless mutant. J. Exp. Zool. 132 (1956), 241-253.