Evidence that Shh cooperates with a retinoic acid inducible co-factor to establish ZPA-like activity

Toshihiko Ogura*, Ignacio S. Alvarez, Astrid Vogel, Concepción Rodríguez, Ronald M. Evans, Juan Carlos Izpisúa Belmonte

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Patterning across the anteroposterior axis of the vertebrate limb bud involves a signal from the polarizing region, a small group of cells at the posterior margin of the bud. Retinoic acid and Sonic hedgehog have been independently postulated as such signals because they can mimic the mirror image digit duplication obtained after grafting polarizing cells to the anterior of limb buds. Here we show that a embryonal carcinoma cell line, P19, transfected with a Shh expression vector shows low polarizing activity, but when cultured with retinoic acid, duplications like those induced by the polarizing region (ZPA) arise. Complete duplications are also obtained by cotransfecting P19 Shh cells with a constitutively active human retinoic acid receptor (VP16-hRARα). These data suggest that Shh and RA cooperate in generating ZPA activity and that Shh, while essential, may not act alone in this process.

Original languageEnglish (US)
Pages (from-to)537-542
Number of pages6
Issue number2
StatePublished - Feb 1996
Externally publishedYes


  • HoxD genes
  • Limb development
  • P19 cells
  • Polarizing activity
  • Retinoic acid
  • Retinoic acid receptors
  • Sonic hedgehog

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology


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