Genetic approaches to understanding brain development: Holoprosencephaly as a model

Holoprosencephaly (HPE) is the most common major developmental defect of th e forebrain in humans. Clinical expression is variable, ranging from a smal l brain with a single cerebral ventricle and cyclopia to clinically unaffec ted carriers in familial HPE. Significant etiologic heterogeneity exists in HPE and includes both genetic and environmental causes. Defects in the cel l signaling pathway involving the Sonic Hedgehog (SHH) gene, as well as def ects in the cholesterol biosynthesis have been shown to cause HPE in humans . More recently, HPE genes from additional signaling pathways have been ide ntified. These discoveries and current genetic approaches serve asa paradig m for studying normal and abnormal brain morphogenesis. (C) 2000 Wiley-Liss , Inc.