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      Roughing up Smoothened: chemical modulators of Hedgehog signaling

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      Journal of Biology

      BioMed Central

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          Abstract

          Small-molecule antagonists of Hedgehog-pathway signaling, such as cyclopamine, have been known for some time. Now, small-molecule agonists of the Hedgehog pathway have also been identified. The finding that both antagonists and agonists target the protein Smoothened supports the emerging hypothesis that Smoothened may be regulated by endogenous small molecules.

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          Most cited references 17

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          Hedgehog signaling in animal development: paradigms and principles.

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            Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function.

            Targeted gene disruption in the mouse shows that the Sonic hedgehog (Shh) gene plays a critical role in patterning of vertebrate embryonic tissues, including the brain and spinal cord, the axial skeleton and the limbs. Early defects are observed in the establishment or maintenance of midline structures, such as the notochord and the floorplate, and later defects include absence of distal limb structures, cyclopia, absence of ventral cell types within the neural tube, and absence of the spinal column and most of the ribs. Defects in all tissues extend beyond the normal sites of Shh transcription, confirming the proposed role of Shh proteins as an extracellular signal required for the tissue-organizing properties of several vertebrate patterning centres.
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              Mutations affecting segment number and polarity in Drosophila

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                Author and article information

                Journal
                J Biol
                Journal of Biology
                BioMed Central (London )
                1478-5854
                1475-4924
                2002
                6 November 2002
                : 1
                : 2
                : 8
                Affiliations
                [1 ]Institute of Chemistry and Cell Biology, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
                1475-4924-1-8
                137068
                12437769
                Copyright © 2002 BioMed Central Ltd
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                Minireview

                Life sciences

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