10.1021/cn900046a.s006 Letian Kuai Letian Kuai Xiang Wang Xiang Wang Jon M. Madison Jon M. Madison Stuart L. Schreiber Stuart L. Schreiber Edward M. Scolnick Edward M. Scolnick Stephen J. Haggarty Stephen J. Haggarty Chemical Genetics Identifies Small-Molecule Modulators of Neuritogenesis Involving Neuregulin-1/ErbB4 Signaling American Chemical Society 2010 phenotypic data PC Nrg 1 nerve growth factor NGF phenotypic consequences oncogene homologue 4 2010-04-21 00:00:00 Dataset https://acs.figshare.com/articles/dataset/Chemical_Genetics_Identifies_Small_Molecule_Modulators_of_Neuritogenesis_Involving_Neuregulin_1_ErbB4_Signaling/2775310 Genetic findings have suggested that neuregulin-1 (Nrg1) and its receptor v-erb-a erythroblastic leukemia viral oncogene homologue 4 (ErbB4) may play a role in neuropsychiatric diseases. However, the downstream signaling events and relevant phenotypic consequences of altered Nrg1 signaling in the nervous system remain poorly understood. To identify small molecules for probing Nrg1−ErbB4 signaling, a PC12-cell model was developed and used to perform a live-cell, image-based screen of the effects of small molecules on Nrg1-induced neuritogenesis. By comparison of the resulting phenotypic data to that of a similar screening performed with nerve growth factor (NGF), this multidimensional screen identified compounds that directly inhibit Nrg1−ErbB4 signaling, such as the 4-anilino-quinazoline Iressa (gefitinib), as well as compounds that potentiate Nrg1−ErbB4 signaling, such as the indolocarbazole K-252a. These findings provide new insights into the regulation of Nrg1−ErbB4 signaling events and demonstrate the feasibility of using such a multidimensional, chemical-genetic approach for discovering probes of pathways implicated in neuropsychiatric diseases.