The Chiari malformation is a developmental defect characterized by abnormal growth of the brainstem and cerebellar herniation. Malformation severity ranges from inconsequential to incapacitating or lethal changes; no genes that are causally involved in these changes have been identified. Here, Xavier Miró and colleagues identify a genetic factor that causes Chiari-like malformations in mice. This factor, Suz12, is a member of a polycomb complex, a group of proteins that act as epigenetic regulators of gene expression. Furthermore, the authors also demonstrate that Zac1, a regulator of neuronal proliferation, is part of the same molecular pathway affected by the Suz12 deficiency. These data help illuminate our understanding of genetic misregulation and how it can cause brain and neural tube defects.

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2009