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However, the molecular mechanism for the innervation patterning has remained elusive. Here, we demonstrate that nardilysin (NRDC,\n                    <jats:italic>Nrdc<\/jats:italic>\n                    ), an enhancer of ectodomain shedding, regulates cardiac sympathetic innervation. Nardilysin\u2010deficient (\n                    <jats:italic>Nrdc<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice show hypoplastic hearts, hypotension, bradycardia, and abnormal sympathetic innervation patterning. While the innervation of left ventricle (LV) of wild\u2010type mice is denser in the subepicardium than in the subendocardium,\n                    <jats:italic>Nrdc<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    LV lacks such a polarity and is uniformly and more abundantly innervated. At the molecular level, the full\u2010length form of p75 neurotrophin receptor (p75\n                    <jats:sup>NTR<\/jats:sup>\n                    ,\n                    <jats:italic>Ngfr<\/jats:italic>\n                    ) is increased in\n                    <jats:italic>Nrdc<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    LV due to the reduced ectodomain shedding of p75\n                    <jats:sup>NTR<\/jats:sup>\n                    . Importantly, the reduction of p75\n                    <jats:sup>NTR<\/jats:sup>\n                    rescued the abnormal innervation phenotype of\n                    <jats:italic>Nrdc<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Moreover, sympathetic neuron\u2010specific, but not cardiomyocyte\u2010specific deletion of\n                    <jats:italic>Nrdc<\/jats:italic>\n                    recapitulated the abnormal innervation patterning of\n                    <jats:italic>Nrdc<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. In conclusion, neuronal nardilysin critically regulates cardiac sympathetic innervation and circulatory dynamics via modulation of p75\n                    <jats:sup>NTR<\/jats:sup>\n                    .\n                  <\/jats:p>","DOI":"10.1096\/fj.202000604r","type":"journal-article","created":{"date-parts":[[2020,7,19]],"date-time":"2020-07-19T11:45:15Z","timestamp":1595159115000},"page":"11624-11640","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Nardilysin controls cardiac sympathetic innervation patterning through regulation of p75 neurotrophin receptor"],"prefix":"10.1096","volume":"34","author":[{"given":"Mikiko","family":"Ohno","sequence":"first","affiliation":[{"name":"Department of Pharmacology Shiga University of Medical Science Otsu Shiga Japan"},{"name":"Department of Cardiovascular Medicine, Graduate School of Medicine Kyoto University Kyoto 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