The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review

Limb Bud

Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Limb Bud


High impact information on Limb Bud

  • The zone of polarizing activity (ZPA) in the posterior limb bud produces Sonic Hedgehog (Shh) protein, which plays a critical role in establishing distinct fates along the anterior-posterior axis [6].
  • Conditional inactivation of Fgf4 reveals complexity of signalling during limb bud development [7].
  • We report here that inactivating Fgf8 in early limb ectoderm causes a substantial reduction in limb-bud size, a delay in Shh expression, misregulation of Fgf4 expression, and hypoplasia or aplasia of specific skeletal elements [8].
  • We demonstrate that Plzf acts as a growth-inhibitory and pro-apoptotic factor in the limb bud [9].
  • We generated a targeted disruption of the mouse Raldh2 gene and found that Raldh2-/- embryos, which die at midgestation without undergoing axial rotation (body turning), exhibit shortening along the anterioposterior axis and do not form limb buds [10].

Chemical compound and disease context of Limb Bud


Biological context of Limb Bud


Anatomical context of Limb Bud

  • FGF8 secreted by the ectoderm then appears to initiate limb bud formation by promoting outgrowth of and Sonic hedgehog expression in the underlying lateral plate mesoderm [21].
  • We have isolated a vertebrate homolog of the Drosophila segment polarity gene hedgehog (hh) from zebrafish and rat, termed vhh-1. vhh-1 is expressed in the node, notochord, floor plate, and posterior limb bud mesenchyme [22].
  • Unexpectedly, when the distribution of Hox-5.2 antigen was compared with that of X1Hbox 1 antigen, a non-overlapping and mutually exclusive pattern was detected (e.g., in developing limb buds, intestine, and somites) [23].
  • These results suggest that early Myf-6 expression may be restricted to a population of myogenic cells that does not contribute to the embryonic muscle masses in limb buds and visceral arches [24].
  • Shortly after implantation, SPC4 transcripts are localized to extraembryonic cell populations, and at later stages are detected in discrete tissues including the primitive gut, heart, neural tube, and limb buds [25].

Associations of Limb Bud with chemical compounds

  • All-trans-retinoic acid (RA) induces striking digit pattern duplications when locally applied to the developing chick limb bud [26].
  • Here we show that the neuronal membrane glycoprotein fasciclin I has a role in the adhesion of sister axons during the development of the grasshopper limb bud [27].
  • Characterization of concentration gradients of a morphogenetically active retinoid in the chick limb bud [28].
  • Limb buds and tails express D2 early and late in metamorphosis, respectively, correlating with the time that these organs undergo TH-induced change [29].
  • The current model suggests that the cholesterol moiety promotes the spread of Shh gradient in the limb bud [30].

Gene context of Limb Bud

  • In situ hybridization of the embryos of these mutants revealed ectopic expression of Shh and fibroblast growth factor-4 (Fgf-4) genes at the anterior margin of limb buds [31].
  • Transcription factor Glioblastoma-3 (Gli3) is cleaved in the anterior region of the limb bud to generate its repressor form [32].
  • Inactivation of Sox9 in limb buds before mesenchymal condensations resulted in a complete absence of both cartilage and bone, but markers for the different axes of limb development showed a normal pattern of expression [33].
  • We expressed the mutant proteins in limb bud micromass culture and treated ATDC5 and C2C12 cells with recombinant GDF5 [34].
  • Strong lacZ expression in embryonic (E) stage E9.5 and E10.5 mouse embryos was found in the limb buds and first and second visceral arches, consistent with the endogenous Dlx3 expression pattern [35].

Analytical, diagnostic and therapeutic context of Limb Bud

  • Transplantation of proximal limb bud tissue into the distal portion of the limb results in a re-expression of Hox-7.1 in the transplanted mesenchyme [36].
  • By immunocytochemistry, we show that CRABP is present at high levels in the progress zone of the limb bud and is distributed across the anteroposterior axis in a gradient with the high point at the anterior margin [37].
  • 2. To investigate the transcript pattern, embryos of various stages were dissected into heads, trunks and limb buds and the RNA was analysed by Northern blotting and RNase protection assays [38].
  • In organ culture demonstrable colony formation by neuroblastoma was likewise inhibited, and conditioned media from one of these embryonic sources (limb bud) slowed but did not abrogate growth of neuroblastoma cells [39].
  • We report static and dynamic light scattering analysis on subpopulations of proteoglycan monomer isolated in milligram quantities from chick limb bud mesenchymal cell cultures by gel fractionation in dissociative solvent conditions [40].


  1. Thalidomide is an inhibitor of angiogenesis. D'Amato, R.J., Loughnan, M.S., Flynn, E., Folkman, J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  2. Identification of a phenotype-specific enhancer in the first intron of the rat collagen II gene. Horton, W., Miyashita, T., Kohno, K., Hassell, J.R., Yamada, Y. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  3. Role of dHAND in the anterior-posterior polarization of the limb bud: implications for the Sonic hedgehog pathway. Fernandez-Teran, M., Piedra, M.E., Kathiriya, I.S., Srivastava, D., Rodriguez-Rey, J.C., Ros, M.A. Development (2000) [Pubmed]
  4. Increasing Fgf4 expression in the mouse limb bud causes polysyndactyly and rescues the skeletal defects that result from loss of Fgf8 function. Lu, P., Minowada, G., Martin, G.R. Development (2006) [Pubmed]
  5. The etiology of the Klippel-Trenaunay syndrome. Baskerville, P.A., Ackroyd, J.S., Browse, N.L. Ann. Surg. (1985) [Pubmed]
  6. Evidence for an expansion-based temporal Shh gradient in specifying vertebrate digit identities. Harfe, B.D., Scherz, P.J., Nissim, S., Tian, H., McMahon, A.P., Tabin, C.J. Cell (2004) [Pubmed]
  7. Conditional inactivation of Fgf4 reveals complexity of signalling during limb bud development. Sun, X., Lewandoski, M., Meyers, E.N., Liu, Y.H., Maxson, R.E., Martin, G.R. Nat. Genet. (2000) [Pubmed]
  8. Fgf8 signalling from the AER is essential for normal limb development. Lewandoski, M., Sun, X., Martin, G.R. Nat. Genet. (2000) [Pubmed]
  9. Plzf regulates limb and axial skeletal patterning. Barna, M., Hawe, N., Niswander, L., Pandolfi, P.P. Nat. Genet. (2000) [Pubmed]
  10. Embryonic retinoic acid synthesis is essential for early mouse post-implantation development. Niederreither, K., Subbarayan, V., Dollé, P., Chambon, P. Nat. Genet. (1999) [Pubmed]
  11. Monoclonal antibodies to different protein-related epitopes of human articular cartilage proteoglycans. Glant, T.T., Mikecz, K., Poole, A.R. Biochem. J. (1986) [Pubmed]
  12. Primary murine limb bud mesenchymal cells in long-term culture complete chondrocyte differentiation: TGF-beta delays hypertrophy and PGE2 inhibits terminal differentiation. Zhang, X., Ziran, N., Goater, J.J., Schwarz, E.M., Puzas, J.E., Rosier, R.N., Zuscik, M., Drissi, H., O'Keefe, R.J. Bone (2004) [Pubmed]
  13. Retinoic acid and 2,3,7,8-tetrachlorodibenzo-p-dioxin selectively enhance teratogenesis in C57BL/6N mice. Birnbaum, L.S., Harris, M.W., Stocking, L.M., Clark, A.M., Morrissey, R.E. Toxicol. Appl. Pharmacol. (1989) [Pubmed]
  14. Liarozole markedly increases all trans-retinoic acid toxicity in mouse limb bud cell cultures: a model to explain the potency of the aromatic retinoid (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylenyl)-1-propenyl] benzoic acid. Pignatello, M.A., Kauffman, F.C., Levin, A.A. Toxicol. Appl. Pharmacol. (2002) [Pubmed]
  15. Cellular anomalies underlying retinoid-induced phocomelia. Zhou, J., Kochhar, D.M. Reprod. Toxicol. (2004) [Pubmed]
  16. Involvement of the Chox-4 chicken homeobox genes in determination of anteroposterior axial polarity during limb development. Nohno, T., Noji, S., Koyama, E., Ohyama, K., Myokai, F., Kuroiwa, A., Saito, T., Taniguchi, S. Cell (1991) [Pubmed]
  17. Prenatal folic acid treatment suppresses acrania and meroanencephaly in mice mutant for the Cart1 homeobox gene. Zhao, Q., Behringer, R.R., de Crombrugghe, B. Nat. Genet. (1996) [Pubmed]
  18. Spatial distribution of cellular protein binding to retinoic acid in the chick limb bud. Maden, M., Ong, D.E., Summerbell, D., Chytil, F. Nature (1988) [Pubmed]
  19. Defects in limb, craniofacial, and thymic development in Jagged2 mutant mice. Jiang, R., Lan, Y., Chapman, H.D., Shawber, C., Norton, C.R., Serreze, D.V., Weinmaster, G., Gridley, T. Genes Dev. (1998) [Pubmed]
  20. Induction of chondrogenesis in limb mesenchymal cultures by disruption of the actin cytoskeleton. Zanetti, N.C., Solursh, M. J. Cell Biol. (1984) [Pubmed]
  21. Roles for FGF8 in the induction, initiation, and maintenance of chick limb development. Crossley, P.H., Minowada, G., MacArthur, C.A., Martin, G.R. Cell (1996) [Pubmed]
  22. Floor plate and motor neuron induction by vhh-1, a vertebrate homolog of hedgehog expressed by the notochord. Roelink, H., Augsburger, A., Heemskerk, J., Korzh, V., Norlin, S., Ruiz i Altaba, A., Tanabe, Y., Placzek, M., Edlund, T., Jessell, T.M. Cell (1994) [Pubmed]
  23. Complementary homeo protein gradients in developing limb buds. Oliver, G., Sidell, N., Fiske, W., Heinzmann, C., Mohandas, T., Sparkes, R.S., De Robertis, E.M. Genes Dev. (1989) [Pubmed]
  24. The muscle regulatory gene, Myf-6, has a biphasic pattern of expression during early mouse development. Bober, E., Lyons, G.E., Braun, T., Cossu, G., Buckingham, M., Arnold, H.H. J. Cell Biol. (1991) [Pubmed]
  25. SPC4, SPC6, and the novel protease SPC7 are coexpressed with bone morphogenetic proteins at distinct sites during embryogenesis. Constam, D.B., Calfon, M., Robertson, E.J. J. Cell Biol. (1996) [Pubmed]
  26. Identification and spatial distribution of retinoids in the developing chick limb bud. Thaller, C., Eichele, G. Nature (1987) [Pubmed]
  27. Laser inactivation of fasciclin I disrupts axon adhesion of grasshopper pioneer neurons. Jay, D.G., Keshishian, H. Nature (1990) [Pubmed]
  28. Characterization of concentration gradients of a morphogenetically active retinoid in the chick limb bud. Eichele, G., Thaller, C. J. Cell Biol. (1987) [Pubmed]
  29. Timing of metamorphosis and the onset of the negative feedback loop between the thyroid gland and the pituitary is controlled by type II iodothyronine deiodinase in Xenopus laevis. Huang, H., Cai, L., Remo, B.F., Brown, D.D. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  30. Cholesterol modification restricts the spread of Shh gradient in the limb bud. Li, Y., Zhang, H., Litingtung, Y., Chiang, C. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  31. A duplicated zone of polarizing activity in polydactylous mouse mutants. Masuya, H., Sagai, T., Wakana, S., Moriwaki, K., Shiroishi, T. Genes Dev. (1995) [Pubmed]
  32. Ski is involved in transcriptional regulation by the repressor and full-length forms of Gli3. Dai, P., Shinagawa, T., Nomura, T., Harada, J., Kaul, S.C., Wadhwa, R., Khan, M.M., Akimaru, H., Sasaki, H., Colmenares, C., Ishii, S. Genes Dev. (2002) [Pubmed]
  33. The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6. Akiyama, H., Chaboissier, M.C., Martin, J.F., Schedl, A., de Crombrugghe, B. Genes Dev. (2002) [Pubmed]
  34. Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2. Seemann, P., Schwappacher, R., Kjaer, K.W., Krakow, D., Lehmann, K., Dawson, K., Stricker, S., Pohl, J., Plöger, F., Staub, E., Nickel, J., Sebald, W., Knaus, P., Mundlos, S. J. Clin. Invest. (2005) [Pubmed]
  35. Genomic structure and functional control of the Dlx3-7 bigene cluster. Sumiyama, K., Irvine, S.Q., Stock, D.W., Weiss, K.M., Kawasaki, K., Shimizu, N., Shashikant, C.S., Miller, W., Ruddle, F.H. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  36. Expression of Hox-7.1 in myoblasts inhibits terminal differentiation and induces cell transformation. Song, K., Wang, Y., Sassoon, D. Nature (1992) [Pubmed]
  37. The role of retinoid-binding proteins in the generation of pattern in the developing limb, the regenerating limb and the nervous system. Maden, M., Ong, D.E., Summerbell, D., Chytil, F. Development (1989) [Pubmed]
  38. Expression pattern of homeobox-containing genes during chick embryogenesis. Wedden, S.E., Pang, K., Eichele, G. Development (1989) [Pubmed]
  39. Widespread inhibition of neuroblastoma cells in the 13- to 17-day-old mouse embryo. Wells, R.S., Miotto, K.A. Cancer Res. (1986) [Pubmed]
  40. Light scattering studies of chick limb bud proteoglycans. Shogren, R., Jamieson, A.M., Blackwell, J., Carrino, D.A., Caplan, A.I. J. Biol. Chem. (1982) [Pubmed]
WikiGenes - Universities