TGIF, a gene associated with human brain defects, regulates neuronal development.

5'-TG-3'-interacting factor (TGIF) is an atypical homeo-domain protein. In vitro studies have shown that TGIF can repress transcription mediated by either of two signaling pathways: TGF-beta and retinoic acid signaling. Mutations in TGIF have been detected in patients with holoprosencephaly (HPE), a severe brain malformation associated with mental retardation.

SONIC HEDGEHOG mutations causing human holoprosencephaly impair neural patterning activity.

Holoprosencephaly (HPE) is a common forebrain malformation associated with mental retardation and craniofacial anomalies. Multiple lines of evidence indicate that loss of ventral neurons is associated with HPE. The condition is etiologically heterogeneous, and abnormalities in any of several genes can cause human HPE.