β1-Integrins Are Critical for Cerebellar Granule Cell Precursor Proliferation

Sandra Blaess, Diana Graus-Porta, Richard Belvindrah, Randor Radakovits, Sebastian Pons, Amanda Littlewood-Evans, Mathias Senften, Huailian Guo, Yuqing Li, Jeffrey H. Miner, Louis F. Reichardt, Ulrich Müller

Research output: Contribution to journalArticle

Abstract

We have previously shown that mice with a CNS restricted knock-out of the integrin β1 subunit gene (Itgb1-CNSko mice) have defects in the formation of lamina and folia in the cerebral and cerebellar cortices that are caused by disruption of the cortical marginal zones. Cortical structures in postnatal and adult Itgb1-CNSko animals are also reduced in size, but the mechanism that causes the size defect has remained unclear. We now demonstrate that proliferation of granule cell precursors (GCPs) is severely affected in the developing cerebellum of Itgb1-CNSko mice. In the absence of β1 expression, GCPs lose contact with laminin in the meningeal basement membrane, cease proliferating, and differentiate prematurely. In vitro studies provide evidence that β1 integrins act at least in part cell autonomously in GCPs to regulate their proliferation. Previous studies have shown that sonic hedgehog (Shh)-induced GCP proliferation is potentiated by the integrin ligand laminin. We show that Shh directly binds to laminin and that laminin-Shh induced cell proliferation is dependent on β1 integrin expression in GCPs. Taken together, these data are consistent with a model in which β1 integrin expression in GCPs is required to recruit a laminin-Shh complex to the surface of GCPs and to subsequently modulate the activity of signaling pathways that regulate proliferation.

Original languageEnglish (US)
Pages (from-to)3402-3412
Number of pages11
JournalJournal of Neuroscience
Volume24
Issue number13
DOIs
StatePublished - Mar 31 2004

Keywords

  • Granule cell precursor
  • Integrin
  • Laminin
  • Proliferation
  • Sonic hedgehog

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Blaess, S., Graus-Porta, D., Belvindrah, R., Radakovits, R., Pons, S., Littlewood-Evans, A., Senften, M., Guo, H., Li, Y., Miner, J. H., Reichardt, L. F., & Müller, U. (2004). β1-Integrins Are Critical for Cerebellar Granule Cell Precursor Proliferation. Journal of Neuroscience, 24(13), 3402-3412. https://doi.org/10.1523/JNEUROSCI.5241-03.2004