{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNeuregulin‐1 (NRG1) is a multifunctional growth factor that plays a critical role in the development and activity of the central nervous system. It regulates neuronal migration, synaptogenesis, myelination, and the modulation of neurotransmitter receptors—including those for glutamate and dopamine—thereby influencing synaptic plasticity and cognitive function. Genetic studies in diverse populations have consistently linked NRG1 risk‐haplotypes and promoter polymorphisms to schizophrenia and related endophenotypes, with altered isoform expression and imbalances in ErbB receptor signaling contributing to abnormalities in cortical circuitry and white matter integrity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its neural functions, aberrant NRG1 signaling is increasingly recognized as a driver of oncogenesis. In several tumor types—including lung adenocarcinoma, thyroid, ovarian, and pancreatic cancers—gene fusion events and dysregulated autocrine or paracrine loops involving NRG1 activate ERBB receptor complexes, thereby promoting cell proliferation, survival, and resistance to targeted therapies. Such findings underscore the therapeutic potential of disrupting NRG1‐mediated signaling in cancers that lack conventional driver alterations."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "33"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nNRG1 signaling is also essential for cardiovascular development and homeostasis as well as peripheral nerve repair. Within the myocardium, NRG1—through activation of ERBB receptors—supports cardiomyocyte survival, adaptive remodeling under stress, and angiogenesis. In the peripheral nervous system, it regulates Schwann cell myelination, ensuring efficient nerve repair following injury."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "34", "end_ref": "38"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional studies reveal that NRG1 influences diverse regulatory processes across tissues. For example, in epithelial cells, spatial segregation of the NRG1 ligand and its receptors modulates activation following injury, while in other contexts, NRG1 stimulation alters intracellular signaling cascades—such as those involving cofilin activation—to affect cytoskeletal dynamics and cell migration. Moreover, variant alleles impacting NRG1 function have been implicated as modifiers in developmental disorders of the enteric nervous system (e.g., Hirschsprung’s disease) and may contribute to conditions like childhood asthma. 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"}, {"type": "b", "children": [{"type": "t", "text": "Neuregulin 1 transcripts are differentially expressed in schizophrenia and regulated by 5' SNPs associated with the disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0602002103"}], "href": "https://doi.org/10.1073/pnas.0602002103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16618933"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16618933"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Gabriel Corfas, Kristine Roy, Joseph D Buxbaum "}, {"type": "b", "children": [{"type": "t", "text": "Neuregulin 1-erbB signaling and the molecular/cellular basis of schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Neurosci (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nn1258"}], "href": "https://doi.org/10.1038/nn1258"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15162166"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15162166"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Alan R Sanders, Jubao Duan, Douglas F Levinson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "No significant association of 14 candidate genes with schizophrenia in a large European ancestry sample: implications for psychiatric genetics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Psychiatry (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1176/appi.ajp.2007.07101573"}], "href": "https://doi.org/10.1176/appi.ajp.2007.07101573"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18198266"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18198266"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Dawei Li, David A Collier, Lin He "}, {"type": "b", "children": [{"type": "t", "text": "Meta-analysis shows strong positive association of the neuregulin 1 (NRG1) gene with schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddl122"}], "href": "https://doi.org/10.1093/hmg/ddl122"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16687441"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16687441"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "R Hashimoto, R E Straub, C S Weickert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression analysis of neuregulin-1 in the dorsolateral prefrontal cortex in schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.mp.4001434"}], "href": "https://doi.org/10.1038/sj.mp.4001434"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14569272"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14569272"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Jeremy Hall, Heather C Whalley, Dominic E Job, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A neuregulin 1 variant associated with abnormal cortical function and psychotic symptoms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Neurosci (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nn1795"}], "href": "https://doi.org/10.1038/nn1795"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17072305"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17072305"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "N M Williams, A Preece, G Spurlock, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Support for genetic variation in neuregulin 1 and susceptibility to schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.mp.4001348"}], "href": "https://doi.org/10.1038/sj.mp.4001348"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12808428"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12808428"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "M R Munafò, D L Thiselton, T G Clark, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Operation of the schizophrenia susceptibility gene, neuregulin 1, across traditional diagnostic boundaries to increase risk for bipolar disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Gen Psychiatry (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/archpsyc.62.6.642"}], "href": "https://doi.org/10.1001/archpsyc.62.6.642"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15939841"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15939841"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "A M McIntosh, T W J Moorhead, D Job, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The effects of a neuregulin 1 variant on white matter density and integrity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.mp.4002103"}], "href": "https://doi.org/10.1038/sj.mp.4002103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17925794"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17925794"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "T L Petryshen, F A Middleton, A Kirby, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Support for involvement of neuregulin 1 in schizophrenia pathophysiology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.mp.4001608"}], "href": "https://doi.org/10.1038/sj.mp.4001608"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15545978"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15545978"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Ke-Xin Li, Ying-Mei Lu, Zheng-Hao Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neuregulin 1 regulates excitability of fast-spiking neurons through Kv1.1 and acts in epilepsy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Neurosci (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nn.3006"}], "href": "https://doi.org/10.1038/nn.3006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22158511"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22158511"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Valgerdur Steinthorsdottir, Hreinn Stefansson, Shyamali Ghosh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multiple novel transcription initiation sites for NRG1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2004.07.029"}], "href": "https://doi.org/10.1016/j.gene.2004.07.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15527969"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15527969"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Xihui Liu, Ryan Bates, Dong-Min Yin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Specific regulation of NRG1 isoform expression by neuronal activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.5317-10.2011"}], "href": "https://doi.org/10.1523/JNEUROSCI.5317-10.2011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21653853"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21653853"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "A J Law, C Shannon Weickert, T M Hyde, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neuregulin-1 (NRG-1) mRNA and protein in the adult human brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuroscience (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuroscience.2004.04.026"}], "href": "https://doi.org/10.1016/j.neuroscience.2004.04.026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15219675"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15219675"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Nicholas C Stefanis, Thomas A Trikalinos, Dimitrios Avramopoulos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impact of schizophrenia candidate genes on schizotypy and cognitive endophenotypes at the population level."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Psychiatry (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopsych.2006.11.015"}], "href": "https://doi.org/10.1016/j.biopsych.2006.11.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17336946"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17336946"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Lyudmila Georgieva, Valentina Moskvina, Tim Peirce, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Convergent evidence that oligodendrocyte lineage transcription factor 2 (OLIG2) and interacting genes influence susceptibility to schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0603029103"}], "href": "https://doi.org/10.1073/pnas.0603029103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16891421"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16891421"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "A P Corvin, D W Morris, K McGhee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Confirmation and refinement of an 'at-risk' haplotype for schizophrenia suggests the EST cluster, Hs.97362, as a potential susceptibility gene at the Neuregulin-1 locus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.mp.4001412"}], "href": "https://doi.org/10.1038/sj.mp.4001412"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14966480"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14966480"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Lynnette Fernandez-Cuesta, Dennis Plenker, Hirotaka Osada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD74-NRG1 fusions in lung adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Discov (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/2159-8290.CD-13-0633"}], "href": "https://doi.org/10.1158/2159-8290.CD-13-0633"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24469108"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24469108"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "J Z Yang, T M Si, Y Ruan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association study of neuregulin 1 gene with schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.mp.4001377"}], "href": "https://doi.org/10.1038/sj.mp.4001377"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12874607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12874607"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Qing Sheng, Xinggang Liu, Eleanor Fleming, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An activated ErbB3/NRG1 autocrine loop supports in vivo proliferation in ovarian cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2009.12.047"}], "href": "https://doi.org/10.1016/j.ccr.2009.12.047"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20227043"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20227043"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Christoph Heining, Peter Horak, Sebastian Uhrig, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccell.2020.06.005"}], "href": "https://doi.org/10.1016/j.ccell.2020.06.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32679108"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32679108"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Timothy R Wilson, Diana Y Lee, Leanne Berry, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neuregulin-1-mediated autocrine signaling underlies sensitivity to HER2 kinase inhibitors in a subset of human cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2011.07.011"}], "href": "https://doi.org/10.1016/j.ccr.2011.07.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21840482"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21840482"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Pei-Wen Tsai, Shine-Gwo Shiah, Ming-Tsan Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Up-regulation of vascular endothelial growth factor C in breast cancer cells by heregulin-beta 1. A critical role of p38/nuclear factor-kappa B signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M204863200"}], "href": "https://doi.org/10.1074/jbc.M204863200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12471041"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12471041"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Saravana M Dhanasekaran, O Alejandro Balbin, Guoan Chen, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Heregulin is sufficient for the promotion of tumorigenicity and metastasis of breast cancer cells in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2003)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12556556"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12556556"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "J Ren, A Bharti, D Raina, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MUC1 oncoprotein is targeted to mitochondria by heregulin-induced activation of c-Src and the molecular chaperone HSP90."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1209012"}], "href": "https://doi.org/10.1038/sj.onc.1209012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16158055"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16158055"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Oghenerukevwe Odiete, Michael F Hill, Douglas B Sawyer "}, {"type": "b", "children": [{"type": "t", "text": "Neuregulin in cardiovascular development and disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.112.267286"}], "href": "https://doi.org/10.1161/CIRCRESAHA.112.267286"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23104879"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23104879"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Wei-Zhong Zhu, Yiheng Xie, Kara White Moyes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neuregulin/ErbB signaling regulates cardiac subtype specification in differentiating human embryonic stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.110.223917"}], "href": "https://doi.org/10.1161/CIRCRESAHA.110.223917"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20671236"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20671236"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Nadia Hedhli, Qunhua Huang, April Kalinowski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endothelium-derived neuregulin protects the heart against ischemic injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCULATIONAHA.110.991125"}], "href": "https://doi.org/10.1161/CIRCULATIONAHA.110.991125"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21555713"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21555713"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Neeraja Syed, Kavya Reddy, David P Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Soluble neuregulin-1 has bifunctional, concentration-dependent effects on Schwann cell myelination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.1681-09.2010"}], "href": "https://doi.org/10.1523/JNEUROSCI.1681-09.2010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20427670"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20427670"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Kristin K Nicodemus, Amanda J Law, Eugenia Radulescu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biological validation of increased schizophrenia risk with NRG1, ERBB4, and AKT1 epistasis via functional neuroimaging in healthy controls."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Gen Psychiatry (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/archgenpsychiatry.2010.117"}], "href": "https://doi.org/10.1001/archgenpsychiatry.2010.117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20921115"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20921115"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Paola D Vermeer, Lisa A Einwalter, Thomas O Moninger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Segregation of receptor and ligand regulates activation of epithelial growth factor receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature01440"}], "href": "https://doi.org/10.1038/nature01440"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12646923"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12646923"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Kyoko Nagata-Ohashi, Yusaku Ohta, Kazumichi Goto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A pathway of neuregulin-induced activation of cofilin-phosphatase Slingshot and cofilin in lamellipodia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200401136"}], "href": "https://doi.org/10.1083/jcb.200401136"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15159416"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15159416"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Maria-Mercè Garcia-Barcelo, Clara Sze-Man Tang, Elly Sau-Wai Ngan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study identifies NRG1 as a susceptibility locus for Hirschsprung's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0809630105"}], "href": "https://doi.org/10.1073/pnas.0809630105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19196962"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19196962"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Nadine Norton, Valentina Moskvina, Derek W Morris, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evidence that interaction between neuregulin 1 and its receptor erbB4 increases susceptibility to schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet B Neuropsychiatr Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.b.30236"}], "href": "https://doi.org/10.1002/ajmg.b.30236"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16249994"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16249994"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "Roger Tavendale, Donald F Macgregor, Somnath Mukhopadhyay, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A polymorphism controlling ORMDL3 expression is associated with asthma that is poorly controlled by current medications."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Allergy Clin Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jaci.2008.01.015"}], "href": "https://doi.org/10.1016/j.jaci.2008.01.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18395550"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18395550"}]}]}]}