Zeb2 Is a Regulator of Astrogliosis and Functional Recovery after CNS Injury
Ana L. Vivinetto,
Il-doo Kim,
David C. Goldberg,
Lilah Fones,
Elizabeth Brown,
Victor S. Tarabykin,
Caitlin E. Hill,
Sunghee Cho,
John W. Cave
Affiliations
Ana L. Vivinetto
Burke Neurological Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA
Il-doo Kim
Burke Neurological Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA
David C. Goldberg
Burke Neurological Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA
Lilah Fones
Burke Neurological Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA
Elizabeth Brown
Burke Neurological Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA
Victor S. Tarabykin
Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Lobachevsky State University of Nizhny Novgorod, Gagarina Ave 23, 603950 Nizhny Novgorod, Russia
Caitlin E. Hill
Burke Neurological Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 1600 York Avenue, New York, NY 10065, USA; Neural Stem Cell Institute, One Discovery Drive, Rensselaer, NY 12144, USA
Sunghee Cho
Burke Neurological Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 1600 York Avenue, New York, NY 10065, USA
John W. Cave
Burke Neurological Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 1600 York Avenue, New York, NY 10065, USA; Department of Chemistry and Life Science, United States Military Academy, West Point, NY 10996, USA; Corresponding author
Summary: The astrocytic response to injury is characterized on the cellular level, but our understanding of the molecular mechanisms controlling the cellular processes is incomplete. The astrocytic response to injury is similar to wound-healing responses in non-neural tissues that involve epithelial-to-mesenchymal transitions (EMTs) and upregulation in ZEB transcription factors. Here we show that injury-induced astrogliosis increases EMT-related genes expression, including Zeb2, and long non-coding RNAs, including Zeb2os, which facilitates ZEB2 protein translation. In mouse models of either contusive spinal cord injury or transient ischemic stroke, the conditional knockout of Zeb2 in astrocytes attenuates astrogliosis, generates larger lesions, and delays the recovery of motor function. These findings reveal ZEB2 as an important regulator of the astrocytic response to injury and suggest that astrogliosis is an EMT-like process, which provides a conceptual connection for the molecular and cellular similarities between astrogliosis and wound-healing responses in non-neural tissue.
