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We found that this loss is caused by excessive apoptosis of sympathetic neuroblasts leading to a failure to generate a normal number of neurons during neurogenesis. NT-3 was also found to be required postnatally. In Nt-3\u2212\/\u2212 mice, sympathetic fibers failed to invade pineal gland and external ear postnatally; whereas other targets of the external and internal carotid nerves, including the submandibular gland and the iris, displayed a normal complement of sympathetic innervation. Sympathetic fibers of mice carrying one functional copy of the Nt-3 gene (Nt-3+\/\u2212 mice) invaded the pineal gland, but failed to branch and form a ground plexus. Cultured neonatal sympathetic neurons responded to NT-3 by neurite outgrowth and mRNA upregulation of the NT-3 receptor, trkC. Exogenously administered NT-3 promoted sympathetic growth and rescued the sympathetic target deficit of the mutant mice. We conclude that NT-3 is required for the survival of sympathetic neuroblasts during neurogenesis and for sympathetic innervation and branching in specific targets after birth.<\/jats:p>","DOI":"10.1242\/dev.122.2.491","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T02:32:32Z","timestamp":1619404352000},"page":"491-500","source":"Crossref","is-referenced-by-count":105,"title":["Prenatal and postnatal requirements of NT-3 for sympathetic neuroblast survival and innervation of specific targets"],"prefix":"10.1242","volume":"122","author":[{"given":"Wael M.","family":"ElShamy","sequence":"first","affiliation":[{"name":"1 Department of Medical Biochemistry and Biophysics, Laboratory of Molecular Neurobiology, Doktorsringen 12A, Karolinska Institute, 171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sten","family":"Linnarsson","sequence":"additional","affiliation":[{"name":"1 Department of Medical Biochemistry and Biophysics, Laboratory of Molecular Neurobiology, Doktorsringen 12A, Karolinska Institute, 171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Fen","family":"Lee","sequence":"additional","affiliation":[{"name":"2 Whitehead Institute for Biomedical Research, and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Jaenisch","sequence":"additional","affiliation":[{"name":"2 Whitehead Institute for Biomedical Research, and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrik","family":"Ernfors","sequence":"additional","affiliation":[{"name":"1 Department of Medical Biochemistry and Biophysics, Laboratory of Molecular Neurobiology, Doktorsringen 12A, Karolinska Institute, 171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1996,2,1]]},"reference":[{"key":"2025021322174585100_DEVELOP_122_2_491C1","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1002\/j.1460-2075.1987.tb04835.x","article-title":"Cellular localization of nerve growth factor synthesis by in situ hybridization","volume":"6","author":"Bandtlow","year":"1987","journal-title":"EMBO J"},{"key":"2025021322174585100_DEVELOP_122_2_491C2","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1002\/j.1460-2075.1982.tb01207.x","article-title":"Purification of a new neurotrophic factor from mammalian brain","volume":"1","author":"Barde","year":"1982","journal-title":"EMBO J"},{"key":"2025021322174585100_DEVELOP_122_2_491C3","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1016\/0896-6273(91)90287-A","article-title":"Neurotrophin-5: A novel neurotrophic factor that activates trk and trkB","volume":"7","author":"Berkemeier","year":"1991","journal-title":"Neuron"},{"key":"2025021322174585100_DEVELOP_122_2_491C4","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1242\/dev.119.3.597","article-title":"Sympathetic neuroblasts undergo a developmental switch in trophic dependence","volume":"119","author":"Birren","year":"1993","journal-title":"Development"},{"key":"2025021322174585100_DEVELOP_122_2_491C5","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/BF00306757","article-title":"A stimulatory effect by nerve growth factor on the regrowth of adrenergic fibres in the mouse peripheral tissues after chemical sympathoectomy with 6-hydroxydopamine","volume":"146","author":"Bjerre","year":"1973","journal-title":"Z. 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