Gene-environmental interaction in early morphogenesis of the brain and developmental anomalies due to its disturbance

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Sonic hedgehog (Shh) is a ventralizing factor in the developing brain. In this study, we showed that Shh is involved in the formation and patterning of the cerebral cortex and the morphogenesis of the ventral part of the eye. Ethanol exposure in early development can result in holoprosencephaly (HPE), which is a developmental anomaly of the forebrain. We used a mouse model of ethanol-induced HPE, and revealed that ethanol activates protein kinase C in the prechordal mesendoderm, thereby impairs the expression of Shh in the embryo and induces HPE malformations.