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Robel, S. ; Bardehle, S. ; Lepier, A.* ; Brakebusch, C.* ; Götz, M.

Genetic deletion of Cdc42 reveals a crucial role for astrocyte recruitment to the injury site in vitro and in vivo.

J. Neurosci. 31, 12471-12482 (2011)

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Open Access Green as soon as Postprint is submitted to ZB.

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It is generally suggested that astrocytes play important restorative functions after brain injury, yet little is known regarding their recruitment to sites of injury, despite numerous in vitro experiments investigating astrocyte polarity. Here, we genetically manipulated one of the proposed key signals, the small RhoGTPase Cdc42, selectively in mouse astrocytes in vitro and in vivo. We used an in vitro scratch assay as a minimal wounding model and found that astrocytes lacking Cdc42 (Cdc42Δ) were still able to form protrusions, although in a nonoriented way. Consequently, they failed to migrate in a directed manner toward the scratch. When animals were injured in vivo through a stab wound, Cdc42Δ astrocytes developed protrusions properly oriented toward the lesion, but the number of astrocytes recruited to the lesion site was significantly reduced. Surprisingly, however, lesions in Cdc42Δ animals, harboring fewer astrocytes contained significantly higher numbers of microglial cells than controls. These data suggest that impaired recruitment of astrocytes to sites of injury has a profound and unexpected effect on microglia recruitment.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Nucleotide-exchance factors; Spinal-cord-injury; Cell polarizatin; Reactive astrocytes; Lentiviral vector; RHO-GTPASES; Polarity proteins; Visual-cortex; Brain; Migration

ISSN (print) / ISBN 0270-6474

e-ISSN 1529-2401

Journal Journal of Neuroscience

Quellenangaben Volume: 31, Issue: 35, Pages: 12471-12482

Publisher Society for Neuroscience

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Stem Cell Research (ISF)