Distinct roles of neuropilin 1 signaling for radial and tangential extension of callosal axons

Authors

  • Yumiko Hatanaka,

    Corresponding author
    1. Department of Molecular Neurobiology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan
    2. Laboratory of Neuroscience, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0178, Japan
    Current affiliation:
    1. Graduate School of Biological Sciences, Nara Institute of Science and Technology, Takayama-cho, Ikoma, Nara 630-0192, Japan
    • Graduate School of Biological Sciences, Nara Institute of Science and Technology, Takayama-cho, Ikoma 630-0192, Japan
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  • Tomoko Matsumoto,

    1. Laboratory of Neuroscience, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0178, Japan
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  • Yuchio Yanagawa,

    1. Department of Genetic and Behavioral Neuroscience, Graduate School of Medicine, Gunma University, Maebashi, Gunma 371-8511, Japan
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  • Hajime Fujisawa,

    1. Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya, Aichi 464-8602, Japan
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  • Fujio Murakami,

    1. Laboratory of Neuroscience, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0178, Japan
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  • Masayuki Masu

    Corresponding author
    1. Department of Molecular Neurobiology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan
    • Department of Molecular Neurobiology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan
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Abstract

Cortical excitatory neurons migrate from their origin in the ventricular zone (VZ) toward the pial surface. During migration, these neurons exhibit a stellate shape in the intermediate zone (IZ), transform into bipolar cells, and then initiate radial migration, extending a trailing process, which may lead to an axon. Here we examined the role of neuropilin 1 (NRP1) in these developmental events. Both NRP1 mRNA and protein were highly expressed in the IZ, where stellate-shaped cells were located. DiI labeling experiments showed that neuronal migration occurred normally in Nrp1 mutant mice up to embryonic day (E) 14.5, the latest day to which the mutant survives, with only subtle axonal defasciculation. However, interference with Nrp1 signaling at a later stage caused pathfinding errors: when a dominant negative form of Nrp1 was electroporated into the cortical VZ cells at E12.5 or E15.5 and examined perinatally, guidance errors were found in tangential axonal extension toward the midline. In contrast, no significant effect was noted on the migration of cortical excitatory neurons. These findings indicate that NRP1 plays an important role in the guidance of callosal axons originating from cortical excitatory neurons but does not support a role in their migration. Moreover, insofar as radial axonal extension within the cortical plate was unaffected, the present findings imply that molecular mechanisms for the axonal extension of excitatory neurons within the cortical plate are distinct from those in the white matter. J. Comp. Neurol. 514:215–225, 2009. © 2009 Wiley-Liss, Inc.

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