Investigating genes regulated by Nrg1 nuclear back signaling.

Nrg1 proteins can be cleaved by gamma secretase in the synaptic membrane. Following cleavage the c-terminal domain of Nrg1 translocates to the nucleus. Which genes are regulated by this signaling is unclear. Here we investigated which genes are regulated. We cultured hippocampal neurons from postnatal day 4 pups. Neurons were cultured for 8 days after which they were either treated with vehicle or the gamma secretase inhibitor DAPT (20uM) overnight. The following day, neurons were either treated with vehicle, soluble ectodomain of ErbB4 (20nM), DAPT (20uM), or DAPT+sErbB4.