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Severe sensory and sympathetic deficits in mice lacking neurotrophin-3

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Abstract

DURING development, neurotrophins help shape the nervous system by regulating neuronal survival and differentiation. Neurotrophin-3 (refs 1–5) is the most abundant neurotrophin during early development6. Neurons responsive to neurotrophin-3 in vitro include primary sensory, sympathetic1–4 motor7, enteric1, locus coeruleus8, hippocampal and cerebellar neurons (ref. 9 for example). Here we report that mice lacking neurotrophin-3 have severe deficits in sensory and sympathetic populations. These mice lack muscle spindles and show abnormal limb positions. In contrast, motor neurons, the enteric nervous system, and the major anatomical regions of the central nervous system seem to develop normally. Comparisons with mutants deficient in other neurotrophins10–12 or their receptors13–15indicate that some neurons require more than one neurotrophin during embryogenesis and suggest that neurotrophin-3 functions by binding receptors in addition to its primary receptor trkC (ref. 16). In particular, neurotrophin-3 is essential for survival of sympathetic and sensory neurons that later become dependent on nerve growth factor or brain-derived neurotrophic factor.

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Authors and Affiliations

  1. Program in Neuroscience, Department of Physiology and University of California School of Medicine, San Francisco, California, 94143-0724, USA

    Isabel Fariñas, Carey Backus, Xiao-Yun Wang & Louis F. Reichardt

  2. Howard Hughes Medical Institute , University of California School of Medicine, San Francisco, California, 94143–0724, USA

    Kevin R. Jones & Louis F. Reichardt

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  1. Isabel Fariñas
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  2. Kevin R. Jones
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  3. Carey Backus
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  4. Xiao-Yun Wang
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  5. Louis F. Reichardt
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Fariñas, I., Jones, K., Backus, C. et al. Severe sensory and sympathetic deficits in mice lacking neurotrophin-3. Nature 369, 658–661 (1994). https://doi.org/10.1038/369658a0

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