Practice question

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 and demonstrated essential role of Sonic hedgehog in midline facial development.