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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Fox, JW; Lamperti, ED; Ekşioğlu, YZ; Hong, SE; Feng, Y; Graham, DA; Scheffer, IE; Dobyns, WB; Hirsch, BA; Radtke, RA; Berkovic, SF; Huttenlocher, PR; Walsh, CA

Published Date

  • December 1998

Published In

Volume / Issue

  • 21 / 6

Start / End Page

  • 1315 - 1325

PubMed ID

  • 9883725

International Standard Serial Number (ISSN)

  • 0896-6273

Digital Object Identifier (DOI)

  • 10.1016/s0896-6273(00)80651-0


  • eng

Conference Location

  • United States