RT Journal Article
SR Electronic
T1 Critical Role of Integrin-Linked Kinase in Granule Cell Precursor Proliferation and Cerebellar Development
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 830
OP 840
DO 10.1523/JNEUROSCI.1852-05.2006
VO 26
IS 3
A1 Julia Mills
A1 Agnieszka Niewmierzycka
A1 Arusha Oloumi
A1 Beatriz Rico
A1 Rene St-Arnaud
A1 Ian R. Mackenzie
A1 Nasrin M. Mawji
A1 Jason Wilson
A1 Louis F. Reichardt
A1 Shoukat Dedhar
YR 2006
UL http://www.jneurosci.org/content/26/3/830.abstract
AB Integrin-linked kinase (ILK) is a serine/threonine protein kinase that plays an important role in integrin signaling and cell proliferation. We used Cre recombinase (Cre)-loxP technology to study CNS restricted knock-out of the ilk gene by either Nestin-driven or gfap-driven Cre-mediated recombination. Developmental changes in ilk-excised brain regions are similar to those observed in mice lacking the integrin β1 subunit in the CNS, including defective laminin deposition, abnormal glial morphology, and alterations in granule cell migration. Decreases in 6-bromodeoxyuridine (BrdU) pulse labeling and proliferating cell nuclear antigen expression in the external granule cell layer of the cerebellum demonstrated that proliferation is disrupted in granule cells lacking ILK. Previous studies have shown that laminin-sonic hedgehog (Shh)-induced granule cell precursor (GCP) proliferation is dependent on β1 integrins, several of which bind laminin and interact with ILK through the β1 cytoplasmic domain. Both ex vivo deletion of ilk and a small molecule inhibitor of ILK kinase activity decreased laminin-Shh-induced BrdU labeling in cultured GCPs. Together, these results implicate ILK as a critical effector in a signaling pathway necessary for granule cell proliferation and cerebellar development.