Practice question

Cyclopia single median eye results from failure of embryonic forebrain to divide into bilateral hemispheres due to deficient midline specification by Sonic hedgehog pathway. Steroidal alkaloid cyclopamine from Veratrum californicum binds Smoothened G-protein coupled receptor blocking hedgehog signal transduction, preventing expression of Pax2 and separation of eye field into two optic vesicles. Lambs whose mothers grazed plant and chick embryos treated experimentally display holoprosencephaly with cyclopia. Classic teratological outbreak traced to cyclopamine led to discovery of hedgehog pathway requirement. Thus teratogen causing cyclopia is cyclopamine potent sonic hedgehog antagonist producing midline facial defect.