Hedgehog signaling in animal development: paradigms and principles

  1. Philip W. Ingham1,3 and
  2. Andrew P. McMahon2,3
  1. 1Centre for Developmental Genetics, University of Sheffield, Sheffield S10 2TN, UK; 2Department of Cellular and Developmental Biology, Harvard University, Cambridge, Massachusetts 02138, USA

This extract was created in the absence of an abstract.

Since their isolation in the early 1990s, members of the Hedgehog family of intercellular signaling proteins have come to be recognized as key mediators of many fundamental processes in embryonic development. Their activities are central to the growth, patterning, and morphogenesis of many different regions within the body plans of vertebrates and insects, and most likely other invertebrates. In some contexts, Hedgehog signals act as morphogens in the dose-dependent induction of distinct cell fates within a target field, in others as mitogens regulating cell proliferation or as inducing factors controlling the form of a developing organ. These diverse functions of Hedgehog proteins raise many intriguing questions about their mode of operation. How do these proteins move between or across fields of cells? How are their activities modulated and transduced? What are their intracellular targets? In this article we review some well-established paradigms of Hedgehog function in Drosophilaand vertebrate development and survey the current understanding of the synthesis, modification, and transduction of Hedgehog proteins.

Embryological studies over much of the last century that relied primarily on the physical manipulation of cells within the developing embryo or fragments of the embryo in culture, provided many compelling examples for the primacy of cell–cell interactions in regulating invertebrate and vertebrate development. The subsequent identification of many of the signaling factors that mediate cellular communication has led to two general conclusions. First, although there are many important signals, most of these fall into a few large families of secreted peptide factors: the Wnt (Wodarz and Nusse 1998), fibroblast growth factor (Szebenyi and Fallon 1999), TGF-β superfamily (Massague and Chen 2000), platelet-derived growth factor (Betsholtz et al. 2001), ephrin (Bruckner and Klein 1998), and Hedgehog families. Second, parallel studies in invertebrate and vertebrate systems have shown that although the final outcome might look quite different …

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