SONIC HEDGEHOG mutations causing human holoprosencephaly impair neural patterning activity.

摘要: Holoprosencephaly (HPE) is a common forebrain malformation associated with mental retardation and craniofacial anomalies. Multiple lines of evidence indicate that loss ventral neurons HPE. The condition etiologically heterogeneous, abnormalities in any several genes can cause human Among these genes, mutations SONIC HEDGEHOG (SHH) are the most commonly identified single gene defect causing SHH mediates number processes central nervous system development required for normal induction cell types brain spinal cord. Although missense have been patients HPE, functional significance has not yet determined. We demonstrate two HPE result decreased vivo activity developing system. These mutant forms fail to regulate properly normally responsive signaling do induce ventrally expressed genes. In addition, immunoreactivity proteins altered, suggesting conformation protein disrupted. studies first demonstration perturb patterning function