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

Motohisa Takahashi, Koji Tamura, Dirk Büscher, Hiroshi Masuya, Sayuri Yonei-Tamura, Ken Matsumoto, Mayumi Naitoh-Matsuo, Jun Takeuchi, Keiko Ogura, Toshihiko Shiroishi, Toshihiko Ogura*, Juan Carlos Izpisúa Belmonte

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

91 Scopus citations


We have determined that Strong's Luxoid (lst(D)) 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 1st(D) 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.

Original languageEnglish (US)
Pages (from-to)4417-4425
Number of pages9
Issue number22
StatePublished - 1998
Externally publishedYes


  • Alx-4
  • Chick
  • Limb development
  • Mouse
  • Polarizing activity
  • shh
  • Stong's Luxoid

ASJC Scopus subject areas

  • Medicine(all)
  • Molecular Biology
  • Developmental Biology

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