The structure and function of genes causing human holoprosencephaly

Abstract

Defective patterning of the ventral forebrain combined with incomplete separation of the eye field during the human embryonic gastrulation and early neurulation stages leads to holoprosencephaly (HPE), the most common malformation of the brain in humans. Both genetic and environmental perturbations can cause this extremely heterogeneous condition. Recently, several genes have been shown to cause HPE in humans including mutations in Sonic Hedgehog, SIX3, ZIC2, and TGIF. Here we summarize the known functions of these factors and discuss the potential roles of additional factors associated with cyclopia in animal models.