Leucine Zipper-Bearing Kinase Is a Critical Regulator of Astrocyte Reactivity in the Adult Mammalian CNS. Academic Article uri icon


  • Reactive astrocytes influence post-injury recovery, repair, and pathogenesis of the mammalian CNS. Much of the regulation of astrocyte reactivity, however, remains to be understood. Using genetic loss and gain-of-function analyses invivo, we show that the conserved MAP3K13 (also known as leucine zipper-bearing kinase [LZK]) promotes astrocyte reactivity and glial scar formation after CNS injury. Inducible LZK gene deletion in astrocytes of adult mice reduced astrogliosis and impaired glial scar formation, resulting in increased lesion size after spinal cord injury. Conversely, LZK overexpression in astrocytes enhanced astrogliosis and reduced lesion size. Remarkably, in the absence of injury, LZK overexpression alone induced widespread astrogliosis inthe CNS and upregulated astrogliosis activators pSTAT3 and SOX9. The identification of LZK as a critical cell-intrinsic regulator of astrocyte reactivity expands our understanding of the multicellular response to CNS injury and disease, with broad translational implications for neural repair.

published proceedings

  • Cell Rep

altmetric score

  • 189.2

author list (cited authors)

  • Chen, M., Geoffroy, C. G., Meves, J. M., Narang, A., Li, Y., Nguyen, M. T., ... Zheng, B.

citation count

  • 31

complete list of authors

  • Chen, Meifan||Geoffroy, Cédric G||Meves, Jessica M||Narang, Aarti||Li, Yunbo||Nguyen, Mallorie T||Khai, Vung S||Kong, Xiangmei||Steinke, Christopher L||Carolino, Krislyn I||Elzière, Lucie||Goldberg, Mark P||Jin, Yishi||Zheng, Binhai

publication date

  • January 2018