Developmental failure of phalanges in the absence of growth/differentiation factor 5

Bone. 2004 Nov;35(5):1069-76. doi: 10.1016/j.bone.2004.06.020.


Growth/differentiation factor 5 (GDF5) is a member of the bone morphogenetic protein (BMP) family, which has been implicated in several skeletogenic events including cartilage and bone formation. To study the role of GDF5, we analyzed digit development in brachypodism (bp) mice, which carry functional null mutations of the Gdf5 gene and exhibit a reduction in the length of digit bones and loss of the middle phalanges. In situ detection of apoptosis and whole-mount detection of cell death showed abnormal apoptosis in the developing phalanges of bp mice. In situ hybridization in bp mice showed overexpression of Gdf5 mRNA in the developing phalanges where apoptotic cells were increased. In addition, bp mice exhibited excessive apoptosis in the interdigital regions. The condensed mesenchymal cells were progressively decreased in the developing phalanges and failed to form cartilage models of the middle phalanges. These findings show that excessive apoptosis in the absence of GDF5 results in developmental failure of the phalanges. We conclude that GDF5 is essential for maintenance and growth of the developing phalanges.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins / deficiency*
  • Bone Morphogenetic Proteins / genetics
  • Bone and Bones / abnormalities
  • Cell Proliferation
  • Forelimb / abnormalities
  • Growth Differentiation Factor 5
  • Hindlimb / abnormalities
  • In Situ Hybridization
  • Limb Deformities, Congenital / genetics*
  • Limb Deformities, Congenital / pathology
  • Mesoderm / cytology
  • Mesoderm / metabolism
  • Mice
  • Mice, Mutant Strains
  • Transforming Growth Factor beta / genetics
  • Up-Regulation / genetics


  • Bmp2 protein, mouse
  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • Gdf5 protein, mouse
  • Growth Differentiation Factor 5
  • Transforming Growth Factor beta