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Mice deficient in NT-3, its tyrosine kinase receptor, TrkC, or in TrkC-positive neuron-specific transcription factor Runx3 display severe ataxia associated with the absence of muscle spindles, and loss of proprioceptive neurons in dorsal root ganglia (DRGs) or their axons (Ernfors et al. 1994; Klein et al. 1994; Tessarollo et al. 1994; Fariñas et al. 1996; Liebl et al. 1997; Inoue et al. 2002; Levanon et al. 2002). NT-3 is expressed in the ventral spinal cord, in the developing limb buds, and in intrafusal bag fibers of muscle spindles later in development (Copray and Brouwer 1994; Fariñas et al. 1996; Tojo et al. 1996). When sensory axons contact developing myotubes, they induce muscle spindle differentiation, forming ring-like spiral nerve endings around them. In the chicken embryo, limb ablations or anti-NT-3 antibody injections into limb buds lead to elimination of TrkC-positive neurons and decreased innervation of motor neurons (Oakley et al. 1995, 1997). 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(NT-3) is a key requirement for the development of proprioceptive inputs to motor neurons (Chen and Frank 1999; Chen et al. 2003). Mice deficient in NT-3, its tyrosine kinase receptor, TrkC, or in TrkC-positive neuron-specific transcription factor Runx3 display severe ataxia associated with the absence of muscle spindles, and loss of proprioceptive neurons in dorsal root ganglia (DRGs) or their axons (Ernfors et al. 1994; Klein et al. 1994; Tessarollo et al. 1994; Fariñas et al. 1996; Liebl et al. 1997; Inoue et al. 2002; Levanon et al. 2002). NT-3 is expressed in the ventral spinal cord, in the developing limb buds, and in intrafusal bag fibers of muscle spindles later in development (Copray and Brouwer 1994; Fariñas et al. 1996; Tojo et al. 1996). When sensory axons contact developing myotubes, they induce muscle spindle differentiation, forming ring-like spiral nerve endings around them. In the chicken embryo, limb ablations or anti-NT-3 antibody injections into limb buds lead to elimination of TrkC-positive neurons and decreased innervation of motor neurons (Oakley et al. 1995, 1997). Is NT-3 only a chemotrophic survival factor for muscle sensory afferents, or does it have additional roles in the development of the proprioceptors and the establishment of the monosynaptic reflex arc? Here we provide evidence that NT-3 acts as a chemoattractant for sensory axons during the final phase of their target-directed pathfinding."}

{"project":"2_test","denotations":[{"id":"15550985-10448156-84929414","span":{"begin":134,"end":138},"obj":"10448156"},{"id":"15550985-12593987-84929415","span":{"begin":152,"end":156},"obj":"12593987"},{"id":"15550985-7514502-84929416","span":{"begin":448,"end":452},"obj":"7514502"},{"id":"15550985-8145824-84929417","span":{"begin":467,"end":471},"obj":"8145824"},{"id":"15550985-7991545-84929418","span":{"begin":491,"end":495},"obj":"7991545"},{"id":"15550985-8982156-84929419","span":{"begin":512,"end":516},"obj":"8982156"},{"id":"15550985-9364058-84929420","span":{"begin":531,"end":535},"obj":"9364058"},{"id":"15550985-12352981-84929421","span":{"begin":550,"end":554},"obj":"12352981"},{"id":"15550985-12093746-84929422","span":{"begin":571,"end":575},"obj":"12093746"},{"id":"15550985-8982156-84929423","span":{"begin":763,"end":767},"obj":"8982156"},{"id":"15550985-8834404-84929424","span":{"begin":781,"end":785},"obj":"8834404"},{"id":"15550985-7789265-84929425","span":{"begin":1121,"end":1125},"obj":"7789265"},{"id":"15550985-9151743-84929426","span":{"begin":1127,"end":1131},"obj":"9151743"},{"id":"T22118","span":{"begin":134,"end":138},"obj":"10448156"},{"id":"T49168","span":{"begin":152,"end":156},"obj":"12593987"},{"id":"T95946","span":{"begin":448,"end":452},"obj":"7514502"},{"id":"T87502","span":{"begin":467,"end":471},"obj":"8145824"},{"id":"T43163","span":{"begin":491,"end":495},"obj":"7991545"},{"id":"T14955","span":{"begin":512,"end":516},"obj":"8982156"},{"id":"T85814","span":{"begin":531,"end":535},"obj":"9364058"},{"id":"T98231","span":{"begin":550,"end":554},"obj":"12352981"},{"id":"T68047","span":{"begin":571,"end":575},"obj":"12093746"},{"id":"T4730","span":{"begin":763,"end":767},"obj":"8982156"},{"id":"T12331","span":{"begin":781,"end":785},"obj":"8834404"},{"id":"T55774","span":{"begin":1121,"end":1125},"obj":"7789265"},{"id":"T805","span":{"begin":1127,"end":1131},"obj":"9151743"}],"text":"Introduction\nNeurotrophin-3 (NT-3) is a key requirement for the development of proprioceptive inputs to motor neurons (Chen and Frank 1999; Chen et al. 2003). Mice deficient in NT-3, its tyrosine kinase receptor, TrkC, or in TrkC-positive neuron-specific transcription factor Runx3 display severe ataxia associated with the absence of muscle spindles, and loss of proprioceptive neurons in dorsal root ganglia (DRGs) or their axons (Ernfors et al. 1994; Klein et al. 1994; Tessarollo et al. 1994; Fariñas et al. 1996; Liebl et al. 1997; Inoue et al. 2002; Levanon et al. 2002). NT-3 is expressed in the ventral spinal cord, in the developing limb buds, and in intrafusal bag fibers of muscle spindles later in development (Copray and Brouwer 1994; Fariñas et al. 1996; Tojo et al. 1996). When sensory axons contact developing myotubes, they induce muscle spindle differentiation, forming ring-like spiral nerve endings around them. In the chicken embryo, limb ablations or anti-NT-3 antibody injections into limb buds lead to elimination of TrkC-positive neurons and decreased innervation of motor neurons (Oakley et al. 1995, 1997). Is NT-3 only a chemotrophic survival factor for muscle sensory afferents, or does it have additional roles in the development of the proprioceptors and the establishment of the monosynaptic reflex arc? Here we provide evidence that NT-3 acts as a chemoattractant for sensory axons during the final phase of their target-directed pathfinding."}