Reactive astrocytes are being considered as therapeutic targets for various neurological disorders [4, 39, 58]. Here, we showed the role of ErbB signaling as a positive upstream regulator in reactive astrogliosis. Different from overexpressing a secreted ligand , we targeted receptors, which specifically regulated the signaling in astrocytes in vivo by using mice genetically engineered for inducible gene expression. We showed that ErbB activation was sufficient to mediate the reactive responses of mature astrocytes, prompting molecular and morphological changes characteristic of injury and disease-induced astrogliosis (Figure 4). We also revealed that many intracellular signals critical for astrogliosis, including STAT3, were stimulated by ErbB activation in astrocytes (Figures 6 and 8). This is in marked contrast to FGF signaling that inhibits astrocyte reactivity , in spite of both ErbB receptors and FGFRs being able to activate similar sets of downstream signaling proteins [15, 16].