Cyclopamine and Jervine block signaling of:
Steroidal alkaloids cyclopamine and jervine from Veratrum californicum lily were identified after epizootics of holoprosencephaly in lambs grazing mountain pastures. They act as direct antagonists of Smoothened transmembrane protein, pivotal transducer of Hedgehog pathway downstream of Patched receptor. Normally Sonic hedgehog binding relieves Patched inhibition of Smoothened allowing Gli activator nuclear translocation. Binding of cyclopamine locks Smoothened inactive conformation, blocking ventral patterning signals in neural tube and face. This Hedgehog blockade explains cyclopia production
Ref: Gilbert, Developmental Biology, 12th ed., Chapter 20: Cyclopamine blocks Sonic hedgehog signaling.
