Mutations in filamin 1 prevent migration of cerebral cortical neurons in human Periventricular heterotopia

Jeremy W. Fox, Edward D. Lamperti, Yaman Z. Ekşioǧlu, Susan E. Hong, Yuanyi Feng, Donna A. Graham, Ingrid E. Scheffer, William B. Dobyns, Betsy A. Hirsch, Rodney A. Radtke, Samuel F. Berkovic, Peter R. Huttenlocher, Christopher A. Walsh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

650 Scopus citations

Abstract

Long-range, directed migration is particularly dramatic in the cerebral cortex, where postmitotic neurons generated deep in the brain migrate to form layers with distinct form and function. In the X-linked dominant human disorder periventricular heterotopia (PH), many neurons fail to migrate and persist as nodules lining the ventricular surface. Females with PH present with epilepsy and other signs, including patent ductus arteriosus and coagulopathy, while hemizygous males die embryonically. We have identified the PH gene as filamin 1 (FLN1), which encodes an actin-cross-linking phosphoprotein that transduces ligand-receptor binding into actin reorganization, and which is required for locomotion of many cell types. FLN1 shows previously unrecognized, high-level expression in the developing cortex, is required for neuronal migration to the cortex, and is essential for embryogenesis.

Original languageEnglish (US)
Pages (from-to)1315-1325
Number of pages11
JournalNeuron
Volume21
Issue number6
DOIs
StatePublished - Dec 1998

ASJC Scopus subject areas

  • Neuroscience(all)

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