Genetic approaches to understanding brain development: holoprosencephaly as a model.
Holoprosencephaly (HPE) is the most common major developmental defect of the forebrain in humans. Clinical expression is variable, ranging from a small brain with a single cerebral ventricle and cyclopia to clinically unaffected carriers in familial HPE. Significant etiologic heterogeneity exists in HPE and includes both genetic and environmental causes. Defects in the cell signaling pathway involving the Sonic Hedgehog (SHH) gene, as well as defects in the cholesterol biosynthesis have been shown to cause HPE in humans. More recently, HPE genes from additional signaling pathways have been identified. These discoveries and current genetic approaches serve as a paradigm for studying normal and abnormal brain morphogenesis. MRDD Research Reviews 6:15-21, 2000.
Muenke
M
M
The Children's Hospital of Philadelphia, Division of Neurology, Philadelphia, Pennsylvania. mmuenke@nhgri.nih.gov
Cohen
M M
MM
D001921:Brain / Q000254:growth & development*; D004777:Environment; D005821:Genetic Techniques; D053823:Hedgehog Proteins; D016142:Holoprosencephaly / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D006801:Humans; D011506:Proteins / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators; D016212:Transforming Growth Factor beta / Q000502:physiology
D053823:Hedgehog Proteins; D011506:Proteins; C509239:SHH protein, human; D015534:Trans-Activators; D016212:Transforming Growth Factor beta