TERATOGEN-MEDIATED INHIBITION OF TARGET TISSUE-RESPONSE TO SHH SIGNALING

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