**Acknowledgments**

**7. Roles of other SOCS proteins in the CNS**

252 Trends in Cell Signaling Pathways in Neuronal Fate Decision

late adult NPC biology.

neural precursor cells [193].

tive NPCs [201].

**8. SOCS proteins and CNS injury**

Other SOCS proteins also have roles in the modulation of signalling in the adult CNS. Other than SOCS2, SOCS3 is the best functionally characterised SOCS protein thus far. SOCS3 plays a role in the regulation of neural stem cell fate. Its overexpression in neural stem cells has been shown to inhibit astrogliogenesis and promote neurogenesis through the inhibition of STAT3 transcriptional activity [156]. More recently, SOCS6 involvement in neuronal dif‐ ferentiation was also established. Exogenous IGF1 was found to enhance neurite outgrowth and dendritic branching of neural stem cells through the induction of SOCS6 expression. The same phenotype was produced independently of IGF-1 by SOCS6 overexpression alone. Similar to SOCS2, SOCS6 is activated through the JAK2/STAT5 pathway, however, in this case it is activated through signalling via the IGF receptor. Activated STAT5 induces SOCS6 expression, which goes on to inhibit STAT5 mediated signalling following the classic nega‐ tive feedback loop [191]. SOCS7 also plays a major role in the brain with SOCS7 null mice exhibiting severe hydrocephalus in early adulthood [192]. While the mechanism by which this occurs has not been elucidated, given the close relationship of ependymal cells and the ventricular space to NPCs in the SVZ, it is tempting to speculate that SOCS7 may also regu‐

SOCS2, SOCS3 and SOCS6 all seem to have potential for use as therapeutic targets involving regulation of NPCs following CNS injury. As described earlier, SOCS2 overexpression in‐ creases the survival of newly born neurons in the adult brain under basal, physiological con‐ ditions. It would therefore be very interesting to look at the effects of SOCS2 overexpression under injury conditions in order to determine whether this phenotype would aid in func‐ tional recovery. Similarly, neurogenesis in an SOCS6 overexpressing system under basal and injury conditions should be examined. SOCS3 does not appear to affect neurogenesis *per se* but instead negatively regulates the proliferative and self-renewal effects of LIF on

SOCS3 has been studied the most extensively under various neural injury conditions, usual‐ ly in concert with effects on neuroinflammation and astrocytes [194-196]. SOCS3 expression is induced or upregulated in various brain regions including hippocampus and lateral ven‐ tricles in response to CNTF administration [197], ischemic stroke [198, 199] and seizure, which also showed transient downregulation of hippocampal SOCS2 expression but no up‐ regulation of SOCS1 [200]. Conversely, after transient forebrain ischemia, SOCS2 expression was upregulated in the hippocampus, not only in astrocytes but also a subset of nestin posi‐

Expression of SOCS molecules following CNS damage has functional consequences. It was proposed that a major contributor to the poor axonal regeneration after injury was a com‐ promised responsiveness to injury-induced growth factors and cytokines [202]. For example, We acknowledge support from Stem Cells Australia and A.M.T. is supported by an NH&MRC Research Fellowship (#628344).
