ADAM17/TACE Inhibits Neurogenesis and Promotes Gliogenesis from Neural Stem Cells

I need a translator for this one but it does sound important.
http://onlinelibrary.wiley.com/doi/10.1002/stem.710/abstract

Abstract

Neural precursor cells (NPC) are activated in CNS injury. However, in spite of being multipotential, their progeny differentiates into astrocytes rather than neurons in situ. We have investigated the role of EGFR in the generation of non-neurogenic conditions. Cultured mouse subventricular zone NPC exposed to differentiating conditions for four days generated ≈50% astrocytes and ≈30%neuroblasts. Inhibition of EGFR with AG1478, significantly increased the number of neuroblasts and decreased that of astrocytes. The same effects were observed upon treatment with the metalloprotease inhibitor GM6001, which prevented endogenous TGF-α release. These results suggested that metalloprotease-dependent EGFR-ligand shedding maintained EGFR activation and favored gliogenesis over neurogenesis. Using ADAM-17 siRNA transfection of NPC, ADAM-17 was identified as the metalloprotease involved in cell differentiation in these cultures. In vivo experiments revealed a significant upregulation of ADAM-17 mRNA and de novo expression of ADAM-17 protein in areas of cortical injury in adult mice. Local NPC, identified by nestin staining, expressed high levels of ADAM-17, as well as TGF-α and EGFR, the three molecules necessary to prevent neurogenesis and promote glial differentiation in vitro. Chronic local infusions of GM6001 resulted in a notable increase in the number of neuroblasts around the lesion. These results indicate that, in vivo, the activation of a metalloprotease, most probably ADAM-17, initiates EGFR-ligand shedding and EGFR activation in an autocrine manner, preventing the generation of new neurons from NPC. Inhibition of ADAM-17, the limiting step in this sequence, may contribute to the generation of neurogenic niches in areas of brain damage.