β1-Integrins Are Critical for Cerebellar Granule Cell Precursor Proliferation
Open Access
- 31 March 2004
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 24 (13), 3402-3412
- https://doi.org/10.1523/jneurosci.5241-03.2004
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 thatβ1 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.Keywords
This publication has 47 references indexed in Scilit:
- Molecular Analysis of Gene Expression in the Developing Pontocerebellar Projection SystemNeuron, 2002
- Conditional Ablation of β1 Integrin in SkinThe Journal of cell biology, 2000
- Integrin SignalingScience, 1999
- THE COMPARTMENTALIZATION OF THE CEREBELLUMAnnual Review of Neuroscience, 1997
- Ice Rhythms—Core Reveals a Plethora of Climate CyclesScience, 1996
- Absence of integrin α6 leads to epidermolysis bullosa and neonatal death in miceNature Genetics, 1996
- Suprabasal integrin expression in the epidermis of transgenic mice results in developmental defects and a phenotype resembling psoriasisCell, 1995
- GABAA Receptor Subtypes Expressed in Cerebellar Granule Cells: A Developmental StudyJournal of Neurochemistry, 1994
- Cerebellar granule cell neurogenesis is regulated by cell-cell interactions in vitroNeuron, 1991
- Influence of Meningeal Cells on the Proliferation of Neuroblasts in CultureDevelopmental Neuroscience, 1981