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Gene Review

GDF5  -  growth differentiation factor 5

Gallus gallus

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Disease relevance of GDF5

  • Taken together, these results support a role for GDF5 in influencing chondrocyte maturation and the induction of hypertrophy in the late stages of embryonic cartilage development, and provide additional mechanistic insights into the role of GDF5 in skeletal development [1].
  • To investigate how GDF-5 controls skeletogenesis, we overexpressed GDF-5 during chick limb development using the retrovirus, RCASBP [2].
  • The capacity of GDF-5 to reduce the requirement of a subpopulation of sensory neurons for NT-3 may have implications for the treatment of peripheral neuropathies [3].

High impact information on GDF5

  • Using in vitro micromass cultures as a model system to study the early steps of chondrogenesis, we show that GDF-5 increases chondrogenesis in a dose-dependent manner [2].
  • In contrast, pulse labelling experiments of GDF-5-infected limbs showed that at later stages of skeletal development GDF-5 can increase proliferation of chondrocytes [2].
  • However, cell suspension cultures showed that GDF-5 might act at these stages by increasing cell adhesion, a critical determinant of early chondrogenesis [2].
  • Analysis of GDF5 and Hoxd11-13 expression in the hindlimb autopod suggests that the forming digit has a digit-one identity [4].
  • In conclusion, this study indicates that GDF-5 is a signal regulated by other BMPs which controls the growth and differentiation of the epiphyses of the digital cartilages acting in close relationship with Hedgehog signaling [5].

Biological context of GDF5

  • At difference with other BMPs, GDF-5 exhibited only a weak cell death promoting effect [5].
  • Potential interactions of GDF-5 with other signals involved in digits morphogenesis were also explored [5].
  • Here, we have studied the function of GDF-5 in digit skeletogenesis by analyzing the effects of its local administration in the developing autopod of embryonic chick and the regulation of its pattern of gene expression by other signals involved in digit morphogenesis [5].
  • Growth/Differentiation Factor 5 (GDF5) plays an important role in limb mesenchymal cell condensation and chondrogenesis [6].
  • Specimens were processed for whole mount in situ hybridization using antisense riboprobes encoding chick GDF-5 and FGF-10 or for histology analysis at indicated time points [7].

Anatomical context of GDF5

  • The interdigital mesoderm in spite of its potential to form ectopic digits with their tendinous apparatus failed to form either ectopic cartilages or ectopic tendons after the implantation of GDF-5 beads in the stages preceding cell death [5].
  • Here, we use a model consisting of long-term, high-density cultures of chick embryonic limb mesenchymal cells, which undergo the entire life history of chondrocyte development, to examine the effects of GDF5 overexpression on chondrocyte maturation [1].
  • These findings suggest gap junction involvement in the action of GDF5 in developmental chondrogenesis [6].
  • Members of the fibroblast growth factor (FGF) family and growth and differentiation factor 5 (GDF-5) have been implicated in joint specification, but their roles in subsequent cavity formation are not defined [8].
  • Subsequently, we over-expressed GDF-5 in the developing chick embryo using a replication competent retrovirus, RCAS(BP) [9].

Other interactions of GDF5


  1. Growth/differentiation factor 5 enhances chondrocyte maturation. Coleman, C.M., Tuan, R.S. Dev. Dyn. (2003) [Pubmed]
  2. Mechanisms of GDF-5 action during skeletal development. Francis-West, P.H., Abdelfattah, A., Chen, P., Allen, C., Parish, J., Ladher, R., Allen, S., MacPherson, S., Luyten, F.P., Archer, C.W. Development (1999) [Pubmed]
  3. Characterization of growth/differentiation factor 5 (GDF-5) as a neurotrophic factor for cultured neurons from chicken dorsal root ganglia. Farkas, L.M., Scheuermann, S., Pohl, J., Unsicker, K., Krieglstein, K. Neurosci. Lett. (1997) [Pubmed]
  4. Manifestation of the limb prepattern: limb development in the absence of sonic hedgehog function. Chiang, C., Litingtung, Y., Harris, M.P., Simandl, B.K., Li, Y., Beachy, P.A., Fallon, J.F. Dev. Biol. (2001) [Pubmed]
  5. Expression and function of Gdf-5 during digit skeletogenesis in the embryonic chick leg bud. Merino, R., Macias, D., Gañan, Y., Economides, A.N., Wang, X., Wu, Q., Stahl, N., Sampath, K.T., Varona, P., Hurle, J.M. Dev. Biol. (1999) [Pubmed]
  6. Functional role of growth/differentiation factor 5 in chondrogenesis of limb mesenchymal cells. Coleman, C.M., Tuan, R.S. Mech. Dev. (2003) [Pubmed]
  7. Roles of FGF-10 on the development of diathrodial limb joints. Lovinescu, I., Koyama, E., Pacifici, M. The Penn dental journal. (2003) [Pubmed]
  8. Differential regulation of GDF-5 and FGF-2/4 by immobilisation in ovo exposes distinct roles in joint formation. Kavanagh, E., Church, V.L., Osborne, A.C., Lamb, K.J., Archer, C.W., Francis-West, P.H., Pitsillides, A.A. Dev. Dyn. (2006) [Pubmed]
  9. Growth/differentiation factor-5 (GDF-5) and skeletal development. Buxton, P., Edwards, C., Archer, C.W., Francis-West, P. The Journal of bone and joint surgery. American volume. (2001) [Pubmed]
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