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Identification of an essential nonneuronal function of neurotrophin 3 in mammalian cardiac development

Nature Genetics volume 14, pages 210–213 (1996)Cite this article

Abstract

Neurotrophin 3 (Nt3) is one of five neurotrophin growth factors which shape the development of the nervous system by regulating neuronal survival and differentiation. Peripheral neuronal subpopulations expressing the TrkC receptor tyrosine kinase respond to Nt3 with enhanced survival, mitogenesis or cell migration1–3 and these neurons are lost in homozygous Nt3 null (−/−) mutant mice4–7. The unexplained perinatal lethality in the Nt3−/− mice, however, suggests a wider function for this neurotrophin. Here we report that Nt3 is essential for the normal development of atria, ventricles, and cardiac outflow tracts. Histological and echocardiographic image analysis of Nt3−/− animals reveal severe cardiovascular abnormalities including atrial and ventricular septal defects, and tetralogy of Fallot, resembling some of the most common congenital malformations in humans. The observed defects are consistent with abnormalities in the survival and/or migration of cardiac neural crest early in embryogenesis8 and establish an essential role for neurotrophin 3 in regulating the development of the mammalian heart.

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Authors and Affiliations

  1. Department of Pathology, Children's Hospital, Boston, Massachusetts, 02115

    Michael J. Donovan

  2. Departmentof Medicine, Cornell University Medical College, New York, New York, 10021, USA

    Rebecca Hahn & Barbara L. Hempstead

  3. Neural Development Group, ABL-Basic Research Program, Frederick Cancer Research and Development Center, P.O.Box B, Frederick, Maryland, 21702, USA

    Lino Tessarollo

Authors
  1. Michael J. Donovan
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  2. Rebecca Hahn
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  3. Lino Tessarollo
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  4. Barbara L. Hempstead
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Donovan, M., Hahn, R., Tessarollo, L. et al. Identification of an essential nonneuronal function of neurotrophin 3 in mammalian cardiac development. Nat Genet 14, 210–213 (1996). https://doi.org/10.1038/ng1096-210

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