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Non-radial tortuous migration with cell polarity alterations of newly generated granule neurons in the neonatal rat dentate gyrus

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Abstract

To establish functional neuronal circuits, newborn neurons generally migrate from the ventricular germinal zones to their final positions during embryonic periods. However, most excitatory neurons of the hippocampal dentate gyrus are born postnatally in the hilus, far from the lateral ventricle. Newly generated granule neurons must then migrate to the surrounding granule cell layer (GCL), which suggests that newborn granule cells may migrate by unique cellular mechanisms. In the present study, we describe the migratory behaviors of postnatally generated granule neurons using combined retroviral labeling and time-lapse imaging analysis. Our results show that whereas half of the newly generated neurons undergo radial migration, the remainder engages in more complex migratory patterns with veering and turning movements accompanied by process formation and cell polarity alterations. These data reveal a previously unappreciated diversity of mechanisms by which granule neurons distribute throughout the GCL to contribute to hippocampal circuitry.

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Acknowledgements

We very thank Drs Hirotaka J. Okano (Keio University) and Robert B. Darnell (The Rockefeller University) for anti-Hu antibody, Nobuaki Tamamaki (Kumamoto University) for the anti-GFP antibody and Hideki Mochizuki (Osaka University) for the retroviral vector. We also thank Dr. Hideo Namiki (Waseda University) for the generous support of this study. We appreciate the review of the manuscript and useful comments on it by Dr. Steven D. Briscoe (Max Planck Institute of Molecular Cell Biology and Genetics).

Funding

TS is supported by JSPS (22500306).

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Conceptualization, TN and TS; formal analysis, TN; investigation, TN and HS; writing—original draft, TN, with input from TS; writing—review and editing, TN and TS; supervision, TS; project administration and funding acquisition, TS.

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Correspondence to Takashi Namba or Tatsunori Seki.

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The authors declare no competing interests.

Research involving human participants and/or animals

All animal experiments were approved by the institutional animal care and use committee at Juntendo University and Tokyo Medical University.

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All experiments were performed on rats.

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Namba, T., Shinohara, H. & Seki, T. Non-radial tortuous migration with cell polarity alterations of newly generated granule neurons in the neonatal rat dentate gyrus. Brain Struct Funct 224, 3247–3262 (2019). https://doi.org/10.1007/s00429-019-01971-0

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  • DOI: https://doi.org/10.1007/s00429-019-01971-0

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