Holoprosencephaly: A Defect in Brain Patterning

Expression and functional analysis of Tgif during mouse midline development

“…HPE is caused by defects in ventral forebrain specification (a part of the anterior axial midline), which lead to incomplete separation of the brain into the left and right hemispheres (Golden, 1998).…”

TGIF Inhibits Retinoid Signaling

“…HPE is a prevalent human genetic disease affecting craniofacial development, with an incidence of up to 1:250 conceptions but, due to a high level of intrauterine lethality, a much lower frequency at birth (12,29). The primary defect in HPE is a failure of the ventral forebrain to divide, with concomitant defects in midline structures which can result in cyclopia and proboscosis (10,37). Many genetic loci have been implicated in HPE, including those encoding the morphogen Sonic Hedgehog (Shh) and the transcription factors Zic2, Six3, and TGIF (29,36).…”

Prenatal diagnosis of holoprosencephaly and ectopia cordis in a twin at 12 weeks' gestation

“…most cases are sporadic. In normal brain development, cells from a certain part of the primitive node migrate anteriorly along the midline, establishing the notochord and the prechordal plate 12,13 . Molecular signals from these midline structures induce the overlying ectoderm to differentiate into a plate of neuroepithelium 12 .…”

“…The process of neurulation converts the neural plate into the neural tube, which is completed at Carnegie stage 12 14 after 5.5 weeks based on the last menstrual period. If the signaling from the notochord or prechordal plate is defective, HPE may develop 13 . Extracranial midline anomalies are commonly associated with HPE (52%) including meningomyelocele, renal dysplasia, omphalocele, esophageal atresia and cardiac defects 15 .…”