Vertebrate limb bud development: Moving towards integrative analysis of organogenesis

Nature Reviews Genetics

Volumn 10, Issue 12, 2009, Pages 845-858

  Zeller, Rolf ^a   López Ríos, Javier ^a   Zuniga, Aimée ^a  

^a UNIVERSITY OF BASEL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

SONIC HEDGEHOG PROTEIN;

ANALYTIC METHOD; CELL DIFFERENTIATION; CELL PROLIFERATION; GENE FUNCTION; GENE INACTIVATION; HUMAN; LIMB BUD; LIMB DEVELOPMENT; LIMB MALFORMATION; MODEL; MORPHOGENESIS; NONHUMAN; ORGANOGENESIS; PHENOTYPE; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; HUMANS; LIMB BUDS; MICE; MODELS, BIOLOGICAL; ORGANOGENESIS; SIGNAL TRANSDUCTION;

MUS; VERTEBRATA;

EID: 70449805406     PISSN: 14710056     EISSN: 14710064     Source Type: Journal    
DOI: 10.1038/nrg2681     Document Type: Review

References (108)

1. Fernandez-Teran, M. & Ros, M. A. The apical ectodermal ridge: morphological aspects and signaling pathways. Int. J. Dev. Biol. 52, 857-871 (2008).
2. King, M., Arnold, J. S., Shanske, A. & Morrow, B. E. T-genes and limb bud development. Am. J. Med. Genet. A 140, 1407-1413 (2006).
3. Zakany, J. & Duboule, D. The role of Hox genes during vertebrate limb development. Curr. Opin. Genet. Dev. 17, 359-366 (2007).
4. Shubin, N., Tabin, C. & Carroll, S. Deep homology and the origins of evolutionary novelty. Nature 457, 818-823 (2009).
5. Saunders, J. W. The proximo-distal sequence of origin of limb parts of the chick wing and the role of the ectoderm. J. Exp. Zool. 108, 363-404 (1948).
6. Summerbell, D., Lewis, J. H. & Wolpert, L. Positional information in chick limb morphogenesis. Nature 244, 492-496 (1973).
7. 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, 579-587 (1993).
8. Lewandoski, M., Sun, X. & Martin, G. R. Fgf8 signalling from the AER is essential for normal limb development. Nature Genet. 26, 460-463 (2000).
9. Mariani, F. V., Ahn, C. P. & Martin, G. R. Genetic evidence that FGFs have an instructive role in limb proximal-distal patterning. Nature 453, 401-405 (2008).
10. Fallon, J. F. et al. FGF-2: apical ectodermal ridge growth factor for chick limb development. Science 264, 104-107 (1994).
11. 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, 739-746 (1995).
12. Kawakami, Y. et al. WNT signals control FGF-dependent limb initiation and AER induction in the chick embryo. Cell 104, 891-900 (2001).
13. Agarwal, P. et al. Tbx5 is essential for forelimb bud initiation following patterning of the limb field in the mouse embryo. Development 130, 623-633 (2003).
14. Benazet, J. D. et al. A self-regulatory system of interlinked signaling feedback loops controls mouse limb patterning. Science 323, 1050-1053 (2009).
15. Sekine, K. et al. Fgf10 is essential for limb and lung formation. Nature Genet. 21, 138-141 (1999).
16. Ohuchi, H. et al. The mesenchymal factor, FGF10, initiates and maintains the outgrowth of the chick limb bud through interaction with FGF8, an apical ectodermal factor. Development 124, 2235-2244 (1997).
17. Sun, X., Mariani, F. V. & Martin, G. R. Functions of FGF signalling from the apical ectodermal ridge in limb development. Nature 418, 501-508 (2002).
18. Dudley, A. T., Ros, M. A. & Tabin, C. J. A re-examination of proximodistal patterning during vertebrate limb development. Nature 418, 539-544 (2002).
19. Mercader, N. et al. Opposing RA and FGF signals control proximodistal vertebrate limb development through regulation of Meis genes. Development 127, 3961-3970 (2000).
20. Capdevila, J., Tsukui, T., Rodriquez Esteban, C., Zappavigna, V. & Izpisúa Belmonte, J. C. Control of vertebrate limb outgrowth by the proximal factor Meis2 and distal antagonism of BMPs by Gremlin. Mol. Cell 4, 839-849 (1999).
21. Niederreither, K., Vermot, J., Schuhbaur, B., Chambon, P. & Dolle, P. Embryonic retinoic acid synthesis is required for forelimb growth and anteroposterior patterning in the mouse. Development 129, 3563-3574 (2002).
22. Yashiro, K. et al. Regulation of retinoic acid distribution is required for proximodistal patterning and outgrowth of the developing mouse limb. Dev. Cell 6, 411-422 (2004).
23. Galloway, J. L., Delgado, I., Ros, M. A. & Tabin, C. J. A reevaluation of X-irradiation-induced phocomelia and proximodistal limb patterning. Nature 460, 400-404 (2009).
24. Zhao, X. et al. Retinoic acid promotes limb induction through effects on body axis extension but is unnecessary for limb patterning. Curr. Biol. 19, 1050-1057 (2009).
25. Tabin, C. & Wolpert, L. Rethinking the proximodistal axis of the vertebrate limb in the molecular era. Genes Dev. 21, 1433-1442 (2007).
26. ten Berge, D., Brugmann, S. A., Helms, J. A. & Nusse, R. Wnt and FGF signals interact to coordinate growth with cell fate specification during limb development. Development 135, 3247-3257 (2008).
27. Hill, T. P., Spater, D., Taketo, M. M., Birchmeier, W. & Hartmann, C. Canonical Wnt/β-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev. Cell 8, 727-738 (2005).
28. Tickle, C. The number of polarizing region cells required to specifiy additional digits in the developing chick wing. Nature 289, 295-298 (1981).
29. Wolpert, L. Positional information and the spatial pattern of cellular differentiation. J. Theor. Biol. 25, 1-47 (1969).
30. Riddle, R. D., Johnson, R. L., Laufer, E. & Tabin, C. Sonic hedgehog mediates the polarizing activity of the ZPA. Cell 75, 1401-1416 (1993).
31. Chiang, C. et al. Manifestation of the limb prepattern: limb development in the absence of sonic hedgehog function. Dev. Biol. 236, 421-435 (2001).
32. Kraus, P., Fraidenraich, D. & Loomis, C. A. Some distal limb structures develop in mice lacking Sonic hedgehog signaling. Mech. Dev. 100, 45-58 (2001).
33. Koshiba-Takeuchi, K. et al. Cooperative and antagonistic interactions between Sall4 and Tbx5 pattern the mouse limb and heart. Nature Genet. 38, 175-183 (2006).
34. Montavon, T., Le Garrec, J. F., Kerszberg, M. & Duboule, D. Modeling Hox gene regulation in digits: reverse collinearity and the molecular origin of thumbness. Genes Dev. 22, 346-359 (2008).
35. Tarchini, B., Duboule, D. & Kmita, M. Regulatory constraints in the evolution of the tetrapod limb anterior-posterior polarity. Nature 443, 985-988 (2006).
36. Capellini, T. D. et al. Pbx1/Pbx2 requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution and Shh expression. Development 133, 2263-2273 (2006).
37. Te Welscher, P., Fernandez-Teran, M., Ros, M. A. & Zeller, R. Mutual genetic antagonism involving GLI3 and dHAND prepatterns the vertebrate limb bud mesenchyme prior to SHH signaling. Genes Dev. 16, 421-426 (2002).
38. Rallis, C., Del Buono, J. & Logan, M. P. Tbx3 can alter limb position along the rostrocaudal axis of the developing embryo. Development 132, 1961-1970 (2005).
39. Yang, Y. et al. Relationship between dose, distance and time in Sonic Hedgehog-mediated regulation of anteroposterior polarity in the chick limb. Development 124, 4393-4404 (1997).
40. 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).
41. Hui, C. & Joyner, A. A mouse model of Greig cephalo-polysyndactyly syndrome: the extra-toesJ mutation contains an intragenic deletion of the Gli3 gene. Nature Genet. 3, 241-246 (1993).
42. Schimmang, T., Lemaistre, M., Vortkamp, A. & Rüther, U. Expression of the zinc finger gene Gli3 is affected in the morphogenetic mouse mutant extra-toes (Xt). Development 11 6, 799-804 (1992).
43. Litingtung, Y., Dahn, R. D., Li, Y., Fallon, J. F. & Chiang, C. Shh and Gli3 are dispensable for limb skeleton formation but regulate digit number and identity. Nature 418, 979-983 (2002).
44. te Welscher, P. et al. Progression of vertebrate limb development through SHH-mediated counteraction of GLI3. Science 298 827-830(2002).
45. Li, Y., Zhang, H., Litingtung, Y. & Chiang, C. Cholesterol modification restricts the spread of Shh gradient in the limb bud. Proc. Natl Acad. Sci. USA 103, 6548-6553 (2006).
46. Ahn, S. & Joyner, A. L. Dynamic changes in the response of cells to positive hedgehog signaling during mouse limb patterning. Cell 11 8, 505-516 (2004).
47. Harfe, B. D. et al. Evidence for an expansion-based temporal Shh gradient in specifying vertebrate digit identities. Cell 11 8, 517-528 (2004).
48. Scherz, P. J., McGlinn, E., Nissim, S. & Tabin, C. J. Extended exposure to Sonic hedgehog is required for patterning the posterior digits of the vertebrate limb. Dev. Biol. 308, 343-354 (2007).
49. Towers, M., Mahood, R., Yin, Y. & Tickle, C. Integration of growth and specification in chick wing digit-patterning. Nature 452, 882-886 (2008).
50. Zhu, J. et al. Uncoupling Sonic hedgehog control of pattern and expansion of the developing limb bud. Dev. Cell 14, 624-632 (2008).
51. Martin, P. Tissue patterning in the developing mouse limb. Int. J. Dev. Biol. 34, 323-336 (1990).
52. Towers, M. & Tickle, C. Growing models of vertebrate limb development. Development 136, 179-190 (2009).
53. 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, 993-1003 (1994).
54. Niswander, L., Jeffrey, S., Martin, G. R. & Tickle, C. A positive feedback loop coordinates growth and patterning in the vertebrate limb. Nature 371, 609-612 (1994).
55. Michos, O. et al. Gremlin-mediated BMP antagonism induces the epithelial-mesenchymal feedback signaling controlling metanephric kidney and limb organogenesis. Development 131, 3401-3410 (2004).
56. Zuniga, A., Haramis, A. P., McMahon, A. P. & Zeller, R. Signal relay by BMP antagonism controls the SHH/ FGF4 feedback loop in vertebrate limb buds. Nature 401, 598-602 (1999).
57. Nissim, S., Hasso, S. M., Fallon, J. F. & Tabin, C. J. Regulation of Gremlin expression in the posterior limb bud. Dev. Biol. 299, 12-21 (2006).
58. Scherz, P. J., Harfe, B. D., McMahon, A. P. & Tabin, C. J. The limb bud Shh-Fgf feedback loop is terminated by expansion of former ZPA cells. Science 305, 396-399 (2004).
59. Verheyden, J. M. & Sun, X. An Fgf/Gremlin inhibitory feedback loop triggers termination of limb bud outgrowth. Nature 454, 638-641 (2008).
60. Zuniga, A. & Zeller, R. Gli3 (Xt) and formin (ld) participate in the positioning of the polarising region and control of posterior limb-bud identity. Development 126, 13-21 (1999).
61. Tickle, C. & Munsterberg, A. Vertebrate limb development-the early stages in chick and mouse. Curr. Opin. Genet. Dev. 11, 476-481 (2001).
62. Zeller, R. & Duboule, D. Dorso-ventral limb polarity and origin of the ridge: on the fringe of independence? Bioessays 19, 541-546 (1997).
63. Arques, C. G., Doohan, R., Sharpe, J. & Torres, M. Cell tracing reveals a dorsoventral lineage restriction plane in the mouse limb bud mesenchyme. Development 134, 3713-3722 (2007).
64. Vargesson, N., Clarke, J. D. W., Vincent, K., Coles, C. & Wolpert, L. Cell fate in the chick limb bud and relationship to gene expression. Development 124, 1909-1918 (1997).
65. Selever, J., Liu, W., Lu, M. F., Behringer, R. R. & Martin, J. F. Bmp4 in limb bud mesoderm regulates digit pattern by controlling AER development. Dev. Biol. 276, 268-279 (2004).
66. Drossopoulou, G. et al. A model for anteroposterior patterning of the vertebrate limb based on sequential long-and short-range Shh signalling and Bmp signalling. Development 127, 1337-1348 (2000).
67. Dahn, R. D. & Fallon, J. F. Interdigital regulation of digit identity and homeotic transformation by modulated BMP signaling. Science 289, 438-441 (2000).
68. Suzuki, T., Hasso, S. M. & Fallon, J. F. Unique SMAD1/5/8 activity at the phalanx-forming region determines digit identity. Proc. Natl Acad. Sci. USA 105, 4185-4190 (2008).
69. Sanz-Ezquerro, J. J. & Tickle, C. Fgf signaling controls the number of phalanges and tip formation in developing digits. Curr. Biol. 13, 1830-1836 (2003).
70. Kawakami, Y. et al. Sall genes regulate region-specific morphogenesis in the mouse limb by modulating Hox activities. Development 136, 585-594 (2009).
71. Macias, D. et al. Role of BMP-2 and OP-1 (BMP-7) in programmed cell death and skeletogenesis during chick limb development. Development 124, 1109-1117 (1997).
72. Bandyopadhyay, A. et al. Genetic analysis of the roles of BMP2, BMP4, and BMP7 in limb patterning and skeletogenesis. PLoS Genet. 2, e216 (2006).
73. Hockman, D. et al. A second wave of Sonic hedgehog expression during the development of the bat limb. Proc. Natl Acad. Sci. USA 105, 16982-16987 (2008).
74. Shapiro, M. D., Hanken, J. & Rosenthal, N. Developmental basis of evolutionary digit loss in the Australian lizard Hemiergis. J. Exp. Zool. B Mol. Dev. Evol. 297, 48-56 (2003).
75. Alberch, P. & Gale, E. A. Size dependence during the development of the amphibian foot. Colchicine-induced digital loss and reduction. J. Embryol. Exp. Morphol. 76, 177-197 (1983).
76. Sakamoto, K. et al. Heterochronic shift in Hox-mediated activation of Sonic hedgehog leads to morphological changes during fin development. PLoS ONE 4, e5121 (2009).
77. Sagai, T. et al. Phylogenetic conservation of a limb-specific, cis-acting regulator of Sonic hedgehog (Shh). Mamm. Genome 15, 23-34 (2004).
78. Cohn, M. J. & Tickle, C. Developmental basis of limblessness and axial patterning in snakes. Nature 399, 474-479 (1999).
79. Boot, M. J. et al. In vitro whole-organ imaging: 4D quantification of growing mouse limb buds. Nature Methods 5, 609-612 (2008).
80. Vokes, S. A., Ji, H., Wong, W. H. & McMahon, A. P. A genome-scale analysis of the cis-regulatory circuitry underlying sonic hedgehog-mediated patterning of the mammalian limb. Genes Dev. 22, 2651-2663 (2008).
81. Tzchori, I. et al. LIM homeobox transcription factors integrate signaling events that control three-dimensional limb patterning and growth. Development 136, 1375-1385 (2009).
82. Mao, J., McGlinn, E., Huang, P., Tabin, C. J. & McMahon, A. P. Fgf-dependent Etv4/5 activity is required for posterior restriction of Sonic hedgehog and promoting outgrowth of the vertebrate limb. Dev. Cell 16, 600-606 (2009).
83. Zhang, Z., Verheyden, J. M., Hassell, J. A. & Sun, X. FGF-regulated Etv genes are essential for repressing Shh expression in mouse limb buds. Dev. Cell 16, 607-613 (2009).
84. Barna, M. & Niswander, L. Visualization of cartilage formation: insight into cellular properties of skeletal progenitors and chondrodysplasia syndromes. Dev. Cell 12, 931-941 (2007).
85. De Robertis, E. M. Spemann's organizer and self-regulation in amphibian embryos. Nature Rev. Mol. Cell Biol. 7, 296-302 (2006).
86. Dessaud, E., McMahon, A. P. & Briscoe, J. Pattern formation in the vertebrate neural tube: a sonic hedgehog morphogen-regulated transcriptional network. Development 135, 2489-2503 (2008).
87. Dessaud, E. et al. Interpretation of the sonic hedgehog morphogen gradient by a temporal adaptation mechanism. Nature 450, 717-720 (2007).
88. Eaton, S. Release and trafficking of lipid-linked morphogens. Curr. Opin. Genet. Dev. 16, 17-22 (2006).
89. Piddini, E. & Vincent, J. P. Interpretation of the wingless gradient requires signaling-induced self-inhibition. Cell 136, 296-307 (2009).
90. Affolter, M. & Basler, K. The Decapentaplegic morphogen gradient: from pattern formation to growth regulation. Nature Rev. Genet. 8, 663-674 (2007).
91. Kicheva, A. et al. Kinetics of morphogen gradient formation. Science 315, 521-525 (2007).
92. Callejo, A., Torroja, C., Quijada, L. & Guerrero, I. Hedgehog lipid modifications are required for Hedgehog stabilization in the extracellular matrix. Development 133, 471-483 (2006).
93. Grandel, H. & Schulte-Merker, S. The development of the paired fins in the zebrafish (Danio rerio). Mech. D e v. 79, 99-120 (1998).
94. Gibert, Y., Gajewski, A., Meyer, A. & Begemann, G. Induction and prepatterning of the zebrafish pectoral fin bud requires axial retinoic acid signaling. Development 133, 2649-2659 (2006).
95. Norton, W. H., Ledin, J., Grandel, H. & Neumann, C. J. HSPG synthesis by zebrafish Ext2 and Extl3 is required for Fgf10 signalling during limb development. Development 132, 4963-4973 (2005).
96. Neumann, C. J., Grandel, H., Gaffield, W., Schulte-Merker, S. & Nusslein-Volhard, C. Transient establishment of anteroposterior polarity in the zebrafish pectoral fin bud in the absence of sonic hedgehog activity. Development 126, 4817-4826 (1999).
97. Prykhozhij, S. V. & Neumann, C. J. Distinct roles of Shh and Fgf signaling in regulating cell proliferation during zebrafish pectoral fin development. BMC Dev. Biol. 8, 91 (2008).
98. Davis, M. C., Dahn, R. D. & Shubin, N. H. An autopodial-like pattern of Hox expression in the fins of a basal actinopterygian fish. Nature 447, 473-476 (2007).
99. Freitas, R., Zhang, G. & Cohn, M. J. Biphasic Hoxd gene expression in shark paired fins reveals an ancient origin of the distal limb domain. PLoS ONE 2, e754 (2007).
100. Case, D. T., Hill, R. J., Merbs, C. F. & Fong, M. Polydactyly in the prehistoric American Southwest. Int. J. Osteoarcheol. 16, 221-235 (2006).
101. Heus, H. C. et al. A physical and transcriptional map of the preaxial polydactyly locus on chromosome 7q36. Genomics 57, 342-351 (1999).
102. Lettice, L. A. et al. Disruption of a long-range cis-acting regulator for Shh causes preaxial polydactyly. Proc. Natl Acad. Sci. USA 99, 7548-7553 (2002).
103. Lettice, L. A. et al. A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly. Hum. Mol. Genet. 12, 1725-1735 (2003).
104. Lettice, L. A., Hill, A. E., Devenney, P. S. & Hill, R. E. Point mutations in a distant sonic hedgehog cis-regulator generate a variable regulatory output responsible for preaxial polydactyly. Hum. Mol. Genet. 17, 978-985 (2008).
105. Park, K., Kang, J., Subedi, K. P., Ha, J.-H. & Park, C. Canine polydactyl mutations with heterogeneous origin in the conserved intronic sequence of Lmbr1 gene. Genetics 179, 2163-2172 (2008).
106. Sagai, T., Hosoya, M., Mizushina, Y., Tamura, M. & Shiroishi, T. Elimination of a long-range cis-regulatory module causes complete loss of limb-specific Shh expression and truncation of the mouse limb. Development 132, 797-803 (2005).
107. Lettice, L. A. & Hill, R. E. Preaxial polydactyly: a model for defective long-range regulation in congenital abnormalities. Curr. Opin. Genet. Dev. 15, 294-300 (2005).
108. Amano, T. et al. Chromosomal dynamics at the Shh locus: limb bud-specific differential regulation of competence and active transcription. Dev. Cell 16, 47-57 (2009).