Proper cerebellar development requires expression of β1-integrin in Bergmann glia, but not in granule neurons

beta 1-class integrins play essential roles both in developmental biology as well as in cancer. Particularly, a Nestin-driven deletion of beta 1-integrin receptors results in severe abnormalities of brain development including a laminar disorganization of cerebellar granule neurons. However, since Nestin is expressed in all kinds of neural precursors, these data do not allow conclusions to be drawn about the role of beta 1-integrins in distinct neuronal and glial cell types. By generating conditional knockout mice using granule cell-specific Math1-promoter sequences, we show here that the expression of beta 1-integrins in granule neurons is dispensable for the development of the cerebellum. Also, deletion of beta 1-integrin from tumors that arise in a mouse model of granule cell precursor-derived medulloblastoma did not result in a significant survival benefit. Last, expression levels of beta 1-integrin in human medulloblastoma samples did not predict patient's outcome. However, a beta 1-integrin knockout using hGFAP-promoter sequences led to cerebellar hypoplasia, inappropriate positioning of Bergmann glia cells in the molecular layer, undirected outgrowth of radial glia fibers, and granule cell ectopia. We therefore conclude that beta 1-integrin expression in cerebellar granule neurons is not essential during normal development or medulloblastoma formation. In fact, it is the expression of beta 1-integrin in glia that is crucial for the proper development of the cerebellar cortex. (C) 2012 Wiley Periodicals, Inc.