Disruption of the Hoxd-13 gene induces localized heterochrony leading to mice with neotenic limbs

Cell. 1993 Nov 5;75(3):431-41. doi: 10.1016/0092-8674(93)90378-4.


Vertebrate Hoxd genes are sequentially activated during the morphogenesis and pattern formation of the limb. Using the approach of gene disruption via homologous recombination in embryonic stem cells, we have assessed the function of the last gene of the complex, Hoxd-13. Mutant mice displayed skeletal alterations along all body axes suggesting the existence of a general multiaxial patterning system. In limbs, abnormalities such as a reduction in the length of some bony elements, loss of phalanges, bone fusions, and the presence of an extra element were observed. We propose that the mutation induces local heterochrony, as illustrated by an important retardation in limb morphogenesis. The relevance of these observations to our understanding of the development and evolution of the tetrapod limb is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone and Bones / abnormalities
  • Calcification, Physiologic / genetics
  • DNA-Binding Proteins / genetics*
  • Extremities / embryology*
  • Genes, Homeobox*
  • Homeodomain Proteins*
  • Limb Deformities, Congenital
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Morphogenesis*
  • Mutagenesis
  • Phenotype
  • Time Factors
  • Transcription Factors*


  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Hoxd13 protein, mouse
  • Transcription Factors