TY - JOUR

T1 - Genetic deletion of cdc42 reveals a crucial role for astrocyte recruitment to the injury site in vitro and in vivo

AU - Robel, Stefanie

AU - Bardehle, Sophia

AU - Lepier, Alexandra

AU - Brakebusch, Cord

AU - Götz, Magdalena

PY - 2011/8/31

Y1 - 2011/8/31

N2 - 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.

AB - 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.

KW - Animals

KW - Animals, Newborn

KW - Astrocytes

KW - Brain Injuries

KW - Cell Movement

KW - Cell Polarity

KW - Cerebral Cortex

KW - Disease Models, Animal

KW - Gene Expression Regulation

KW - Green Fluorescent Proteins

KW - In Situ Nick-End Labeling

KW - In Vitro Techniques

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Nerve Tissue Proteins

KW - Time Factors

KW - cdc42 GTP-Binding Protein

U2 - 10.1523/JNEUROSCI.2696-11.2011

DO - 10.1523/JNEUROSCI.2696-11.2011

M3 - Journal article

C2 - 21880909

VL - 31

SP - 12471

EP - 12482

JO - The Journal of neuroscience : the official journal of the Society for Neuroscience

JF - The Journal of neuroscience : the official journal of the Society for Neuroscience

SN - 0270-6474

IS - 35

ER -