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

β1-class integrins play essential roles both in developmental biology as well as in cancer. Particularly, a Nestin-driven deletion of β1-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 β1-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 β1-integrins in granule neurons is dispensable for the development of the cerebellum. Also, deletion of β1-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 β1-integrin in human medulloblastoma samples did not predict patient's outcome. However, a β1-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 β1-integrin expression in cerebellar granule neurons is not essential during normal development or medulloblastoma formation. In fact, it is the expression of β1-integrin in glia that is crucial for the proper development of the cerebellar cortex.
(Copyright © 2012 Wiley Periodicals, Inc.)