Practice question

Sonic hedgehog morphogen produced by prechordal mesoderm and ventral midline is essential for frontonasal prominence outgrowth and medial facial development. Alcohol consumption during critical gastrulation window impairs cholesterol modification of Shh protein necessary for signaling potency and reduces Shh transcription via oxidative injury to midline cells. Mouse models show ethanol exposure decreases Shh mRNA in frontonasal ectoderm leading to reduced proliferation and increased apoptosis of facial mesenchyme, phenotypes rescued by Shh agonists or cholesterol supplementation. Reduced Shh expression therefore mediates midfacial hypoplasia, holoprosencephaly spectrum features observed in fetal alcohol syndrome pathogenesis.