One-Eyed Animals Implicate Cholesterol in Development Science. June 5, 1998 (Excerpt)   In ancient times, Homer depicted the one-eyed Cyclops as a terrifying and mysterious monster. Today we recognize infants born with a single large eye as victims of a birth defect called cyclopia, which derails the normal development of the brain and face. Cyclopia and milder forms of the same developmental disorder result from a failure of the embryonic forebrain to subdivide properly. Defective genes can disrupt this process in people and animals, but so can certain toxins, some of them found in wild plants. Research by Phillip Beachy, a molecular biologist at The Johns Hopkins University School of Medicine in Baltimore, and his colleagues, and similar experiments by a second group at the University of Washington (UW), indicate that these toxins may interrupt a critical developmental signal, perhaps because they interfere with the normal traffic of cholesterol in cells. A disruption in cholesterol transport may prevent embryonic cells from heeding signals involving a protein called Sonic hedgehog (Shh). These findings provide some of the first, clear evidence that cholesterol, long known as a structural component of cell membranes and as the raw material that the body converts into steroid hormones and bile acids, can also influence the signaling paths that guide development. The toxin compounds that cause cyclopia resemble cholesterol in structure, according to Beachy's group and the UW team of John Incardona, Raj Kapur, and Henk Roelink. These researchers found that these natural compounds render cells that receive the Shh signal unable to respond properly. The toxins are produced in high concentrations by plants in the genus Veratrum, also known as corn lily. Ewes that eat these plants produce a high percentage of lambs suffering from severe cyclopia. About one in 16,000 babies is born with some form of cyclopia, technically known as holoprosencephaly (HPE). Early in pregnancy, before nature exerts quality control and flawed embryos are spontaneously aborted, the rate is much higher: one in 250. People with the mildest form of the disorder may have signs as minor as a single front incisor; severe cases are marked by one eye in the middle of the face, below a protruding nasal structure, and serious brain abnormalities. Infants with full-blown cyclopia die soon after birth. Note: The work of the UW researchers was supported in part by the UW NIEHS Center for Ecogenetics and Environmental Health through a pilot project grant: Role of Sonic hedgehog in cyclopamine-induced holoprosencephaly.