Integrin-linked kinase regulates Bergmann glial differentiation during cerebellar development

Richard Belvindrah, Perihan Nalbant, Sheng Ding, Chuanyue Wu, Gary M. Bokoch, Ulrich Müller

Research output: Contribution to journalArticlepeer-review

Abstract

We demonstrate here that integrin-linked kinase (ILK), a serine/threonine kinase that binds to the β1 integrin cytoplasmic domain, regulates cerebellar development. Mice with a CNS-restricted knock-out of the Ilk gene show perturbations in the laminar structure of the cerebellar cortex that are associated with defects in Bergmann glial fibers and the formation of meningeal basement membranes. Similar defects have been observed in mice lacking β1 integrins in the CNS. ILK and β1 integrins are coexpressed in Bergmann glial cells, and studies with primary cells in culture demonstrate that ILK and CDC42 are required for β1-integrin-dependent glial process outgrowth. Consistent with these findings, the amount of GTP-bound CDC42 is impaired in the cerebellum of Ilk-deficient mice. We conclude that β1 integrin, ILK and CDC42 are components of the signaling machinery that regulates glial process outgrowth in the cerebellum. We also show that granule cell precursor proliferation is affected in ILK-deficient mice, but our findings provide strong evidence that proliferative defects are a secondary consequence of ILK function in glia.

Original languageEnglish (US)
Pages (from-to)109-125
Number of pages17
JournalMolecular and Cellular Neuroscience
Volume33
Issue number2
DOIs
StatePublished - Oct 2006
Externally publishedYes

Keywords

  • Bergmann glia
  • Cerebellum
  • Extracellular matrix
  • ILK
  • Integrin

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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