Cell

Cell

Volume 75, Issue 7, 31 December 1993, Pages 1401-1416
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Article
Sonic hedgehog mediates the polarizing activity of the ZPA

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Abstract

The zone of polarizing activity (ZPA) is a region at the posterior margin of the limb bud that induces mirror-image duplications when grafted to the anterior of a second limb. We have isolated a vertebrate gene, Sonic hedgehog, related to the Drosophila segment polarity gene hedgehog, which is expressed specifically in the ZPA and in other regions of the embryo, that is capable of polarizing limbs in grafting experiments. Retinoic acid, which can convert anterior limb bud tissue into tissue with polarizing activity, concomitantly induces Sonic hedgehog expression in the anterior limb bud. Implanting cells that express Sonic hedgehog into anterior limb buds is sufficient to cause ZPA-like limb duplications. Like the ZPA, Sonic hedgehog expression leads to the activation of Hox genes. Sonic hedgehog thus appears to function as the signal for anteroposterior patterning in the limb.

References (61)

  • C.J. Tabin

    Retinoids, homeoboxes, and growth factors: toward molecular models for limb development

    Cell

    (1991)
  • A.M. Taylor et al.

    Contrasting distributions of patched and hedgehog proteins in the Drosophila embryo

    Mech. Dev.

    (1993)
  • C. Tickle et al.

    A quantitative analysis of the effect of all-trans-retinoic acid on the pattern of chick wing development

    Dev. Biol.

    (1985)
  • L. Wolpert

    Positional information and the spatial pattern of cellular differentiation

    J. Theor. Biol.

    (1969)
  • F.M. Ausubel et al.

    Current Protocols in Molecular Biology

    (1989)
  • J.P. Brockes

    We may not have a morphogen

    Nature

    (1991)
  • J. Devereux et al.

    A comprehensive set of sequence analysis programs for the VAX

    Nucl. Acids Res.

    (1984)
  • W. Driever et al.

    The bicoid protein is a positive regulator of hunchback transcription in early Drosophila embryo

    Nature

    (1989)
  • P. Dolle et al.

    Coordinate expression of the murine Hox-5 complex homeobox-containing genes during limb pattern formation

    Nature

    (1989)
  • Y. Echelard et al.

    Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity

    Cell

    (1993)
  • D. Fekete et al.

    Replication-competent retroviral vectors encoding alkaline phosphatase reveal spatial restriction of viral gene expression/transduction in the chick embryo

    Mol. Cell. Biol.

    (1993)
  • D. Fekete et al.

    Retroviral infection coupled with tissue transplantation limits gene transfer in the chicken embryo

  • V. Hamburger et al.

    A series of normal stages in the development of the chick embryo

    J. Exp. Morph.

    (1951)
  • L.S. Honig et al.

    Maps of strength of positional signalling activity in the developing chick wing bud

    J. Embryol. Exp. Morph.

    (1985)
  • A. Hornbruch et al.

    Positional signalling by Hensen's node when grafted to the chick limb bud

    J. Embryol. Exp. Morph.

    (1986)
  • A. Hornbruch et al.

    The spatial and temporal distribution of polarizing activity in the flank of the pre-limb bud stages in the chick embryo

    Development

    (1991)
  • S.H. Hughes et al.

    Adaptor plasmids simplify the insertion of foreign DNA into helper-independent retroviral vectors

    J. Virol.

    (1987)
  • P.W. Ingham

    The molecular genetics of embryonic pattern formation in Drosophila

    Nature

    (1988)
  • J.C. Izpisua-Belmonte et al.

    Expression of the homeobox Hox-4 genes and the specification of position in chick wing development

    Nature

    (1991)
  • M. Kozak

    An analysis of 5′-noncoding sequences from 699 vertebrate messenger RNAs

    Nucl. Acids Res.

    (1987)

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