Glial cells missing 1 triggers gliosis and angiogenesis after neonatal brain injury

The glial cells missing (Gcm) protein in <i>Drosophila</i> plays a crucial role in the cell fate switch in the nervous system and in induction of glial cell differentiation. However, the functions of the mammalian homolog Gcm1 in normal neural development and pathological conditions remain elusive. Here, we report that <i>Gcm1</i> was upregulated in Nestin⁺ cells immediately after neonatal brain injury, followed by accumulation of GFAP⁺ and Olig2⁺ cells in the penumbra region. Injury-induced upregulation of <i>Lif</i> gene was mediated, at least in part, by the demethylation activity of Gcm1. In addition, Gcm1 strongly induced angiogenesis in the injury lesion as well as in the developing brain via vascular endothelial growth factor A and C activity. Lack of <i>Gcm1</i>-mediated angiogenesis could be a major cause of the dysplasia in placental labyrinths found in <i>Gcm1</i> ^-/- embryos, leading to embryonic lethality. Our data suggest that <i>Gcm1</i> triggers both gliosis and angiogenesis after brain injury and could be a target for therapeutic intervention.