Practice question

Sonic hedgehog signaling involves cholesterol-modified ligand binding Patched relieving inhibition of Smoothened GPCR-like protein, activating GLI transcription for ventral patterning, limb bud and organogenesis. Cyclopamine is steroidal alkaloid from Veratrum californicum acting as Smoothened antagonist, binding transmembrane domain preventing downstream GLI activation. Ingestion during pregnancy causes holoprosencephaly and cyclopia in lambs. Alcohol, BPA and retinoic acid teratogens act via different pathways: alcohol disrupts L1CAM and Shh indirectly, BPA via estrogen receptors, retinoic acid via HOX dysregulation. Cyclopamine is canonical specific chemical probe that experimentally blocks Shh, used to model Shh deficiency disorders and study morphogen gradients.