The role of Alx-4 in the establishment of anteroposterior polarity during vertebrate limb development

Development. 1998 Nov;125(22):4417-25. doi: 10.1242/dev.125.22.4417.


We have determined that Strong's Luxoid (lstJ) [corrected] mice have a 16 bp deletion in the homeobox region of the Alx-4 gene. This deletion, which leads to a frame shift and a truncation of the Alx-4 protein, could cause the polydactyly phenotype observed in lstJ [corrected] mice. We have cloned the chick homologue of Alx-4 and investigated its expression during limb outgrowth. Chick Alx-4 displays an expression pattern complementary to that of shh, a mediator of polarizing activity in the limb bud. Local application of Sonic hedgehog (Shh) and Fibroblast Growth Factor (FGF), in addition to ectodermal apical ridge removal experiments suggest the existence of a negative feedback loop between Alx-4 and Shh during limb outgrowth. Analysis of polydactylous mutants indicate that the interaction between Alx-4 and Shh is independent of Gli3, a negative regulator of Shh in the limb. Our data suggest the existence of a negative feedback loop between Alx-4 and Shh during vertebrate limb outgrowth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Body Patterning*
  • Chick Embryo
  • Cloning, Molecular
  • DNA-Binding Proteins
  • Extremities / embryology*
  • Extremities / surgery
  • Feedback
  • Fibroblast Growth Factors
  • Hedgehog Proteins
  • Homeodomain Proteins / genetics*
  • Kruppel-Like Transcription Factors
  • Limb Deformities, Congenital*
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Nerve Tissue Proteins*
  • Polydactyly / genetics
  • Proteins
  • Repressor Proteins*
  • Sequence Analysis, DNA
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Species Specificity
  • Tissue Transplantation
  • Trans-Activators*
  • Transcription Factors
  • Xenopus Proteins*
  • Zinc Finger Protein Gli3


  • Alx4 protein, mouse
  • DNA-Binding Proteins
  • GLI3 protein, Xenopus
  • GLI3 protein, human
  • Gli3 protein, mouse
  • Hedgehog Proteins
  • Homeodomain Proteins
  • Kruppel-Like Transcription Factors
  • Nerve Tissue Proteins
  • Proteins
  • Repressor Proteins
  • SHH protein, human
  • Trans-Activators
  • Transcription Factors
  • Xenopus Proteins
  • Zinc Finger Protein Gli3
  • Fibroblast Growth Factors

Associated data

  • GENBANK/AF092538