Tuyển tập các báo cáo nghiên cứu về sinh học được đăng trên tạp chí sinh học Journal of Biology đề tài: Roughing up Smoothened: chemical modulators of Hedgehog signaling. | J. Biol. Journal of Biology BioMed Central Minireview Roughing up Smoothened chemical modulators of Hedgehog signaling Randall W King Address Institute of Chemistry and Cell Biology Department of Cell Biology Harvard Medical School Boston MA 02115 USA. E-mail randy_king@ Published 6 November 2002 Journal of Biology 2002 1 8 The electronic version of this article is the complete one and can be found online at http content l 2 8 2002 BioMed Central Ltd ISSN 1475-4924 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. Thirty years before genetic experiments in Drosophila created the hedgehog mutant 1 a naturally occurring chemical genetic experiment had produced sheep with an even more disturbing phenotype cyclopia. The lack of midline facial structures in the offspring of grazing sheep in the western United States was attributed to ingestion of the lily Veratrum californicum and subsequent work identified the jervine family of steroidal alkaloids including the compound cyclopamine as the teratogens responsible for the striking effects 2 . Insights into a possible mechanism of action did not emerge until the mid 1990s when it was discovered that mutation of the Sonic hedgehog Shh gene in mice 3 or humans 4 could produce defects that resembled those caused by administration of cyclopamine to animals. Shh is a secreted protein ligand that like other members of the Hedgehog Hh family activates the Hh signal transduction pathway and plays an important role in patterning many tissues 5 . The similarity in phenotypes suggested that teratogens might induce cyclopia by antagonizing the Hh pathway and this hypothesis was confirmed when it
