The suppression of WNK1 expression by RNA interference has been
shown to promote neurite extension and eliminate the inhibitory response
to Nogo signaling in cortical cultured neurons [35]. In addition,
the overexpression of WNK1 (123-510) reduces Nogo-induced inhibition
of neurite extension rather than strengthening it, and inhibits the
activation of RhoA [35]. Previous studies have shown that WNK1 is a
negative regulator of cell growth via phosphorylation by the PI3-K/Akt
signaling pathway [36],which is largely implicated in the schizophrenia
pathophysiology. Furthermore, disruption of the WNK1 gene in mice
leads to death of the embryo at day 13 [23–25], suggesting an essential
role of WNK1 in embryonic and neural development, which is a critical
period implicated in schizophrenia.