Neuregulin1 nuclear signaling influences adult neurogenesis and regulates a schizophrenia susceptibility gene network within the mouse dentate gyrus.

Neuregulin1 (Nrg1) signaling is critical for aspects of neuronal development and function from fate specification to synaptic plasticity. Type III Nrg1 is a synaptic protein which engages in bi-directional signaling with its receptor ErbB4. Forward signaling engages ErbB4 phosphorylation, whereas back signaling engages two known mechanisms: 1. local axonal PI3K-AKT signaling, and 2. cleavage by gamma secretase resulting in cytosolic release of the intracellular domain (ICD), which can traffic to the nucleus (Bao, Wolpowitz et al. 2003, Hancock, Canetta et al. 2008). To dissect the contribution of these alternate signaling strategies to neuronal development we generated a transgenic mouse with a missense mutation (V