Teratogen-mediated inhibition of target tissue response to Shh signaling.

Cooper MK, Porter JA, Young KE, Beachy PA
Science. 1998 280 (5369): 1603-7

PMID: 9616123 · DOI:10.1126/science.280.5369.1603

Veratrum alkaloids and distal inhibitors of cholesterol biosynthesis have been studied for more than 30 years as potent teratogens capable of inducing cyclopia and other birth defects. Here, it is shown that these compounds specifically block the Sonic hedgehog (Shh) signaling pathway. These teratogens did not prevent the sterol modification of Shh during autoprocessing but rather inhibited the response of target tissues to Shh, possibly acting through the sterol sensing domain within the Patched protein regulator of Shh response.

MeSH Terms (30)

Abnormalities, Drug-Induced Animals Cell Membrane Central Nervous System Chick Embryo Cholesterol Culture Techniques DNA-Binding Proteins Endoplasmic Reticulum Hedgehog Proteins Hepatocyte Nuclear Factor 3-beta Holoprosencephaly Homeodomain Proteins LIM-Homeodomain Proteins Membrane Proteins Muscle Proteins Nerve Tissue Proteins Nuclear Proteins Patched Receptors PAX7 Transcription Factor Proteins Receptors, Cell Surface Signal Transduction Teratogens Tomatine trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride Trans-Activators Transcription Factors Triparanol Veratrum Alkaloids

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