Mutations in human DISC1, a protein associated with the dynein motor complex, have been implicated in schizophrenia. In mouse, knockdown of DISC1 causes a number of phenotypes, including premature neuronal differentiation and impaired neurite and axonal outgrowth, while Disc1 mutants, although viable and fertile, show strong behavioural defects. However, the potential functions of DISC1 in glia, including astrocytes, have been less studied, even though disruption of astrocytes has been reported in schizophrenic patients. Jianwei Jiao and co-workers (p. ) therefore set out to assess the consequences of Disc1 loss- or gain-of-function in mouse astrocytes. Both in vivo and in vitro, they find that Disc1 depletion impairs astrogenesis, while overexpression promotes differentiation down the astrocyte lineage. Mechanistically, the authors show that DISC1 modulates RAS/MEK/ERK signalling, which is known to be important for astrogenesis: upon Disc1 deletion, MEK and ERK phosphorylation (and hence activation) is impaired. In this context, interaction between DISC1 and the RAS-association domain protein RASSF7 appears to be important: as with DISC1, overexpression of RASSF7 promotes astrocyte differentiation. Although the potential contribution of this astrogenic activity of DISC1 to the schizophrenia phenotype has yet to be analysed, these data suggest that modulation of astrocyte differentiation may be relevant for this neuropsychiatric disorder.
