Proteomic and transcriptomic analysis of Id2- and Ascl4-induced wiring in adult hippocampal granule cells

Recent studies have shown that molecular programming by basic helix-loop-helix (bHLH) proteins can reactivate wiring in adult neurons. Meanwhile circuit analyses in these studies demonstrated functional circuit formation, the underlying molecular mechanisms remain elusive. Here, we used RNAseq, mass-spectrometry, and immunohistochemistry to investigate the transcriptomic and proteomic consequences of Id2 (a regulator of bHLH transcription factors) and Ascl4 (a bHLH transcription factor)-induced wiring in adult hippocampal granule cells, which lead to the formation of mainly feedback and feedforward circuits, respectively. As a common feature, we identified a set of proteins that are co-regulated by Id2 and Ascl4. In addition, we identified proteomic changes, which may originate from surrounding brain cells and play a role in the coordination of wiring. Together, our results provide support for the hypothesis that adult wiring is controlled by specific molecular programs.