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Nitric oxide stimulates human neural progenitor cell migration via cGMP-mediated signal transduction

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Abstract

Neuronal migration is one of the most critical processes during early brain development. The gaseous messenger nitric oxide (NO) has been shown to modulate neuronal and glial migration in various experimental models. Here, we analyze a potential role for NO signaling in the migration of fetal human neural progenitor cells. Cells migrate out of cultured neurospheres and differentiate into both neuronal and glial cells. The neurosphere cultures express neuronal nitric oxide synthase and soluble guanylyl cyclase that produces cGMP upon activation with NO. By employing small bioactive enzyme activators and inhibitors in both gain and loss of function experiments, we show NO/cGMP signaling as a positive regulator of migration in neurosphere cultures of early developing human brain cells. Since NO signaling regulates cell movements from developing insects to mammalian nervous systems, this transduction pathway may have evolutionary conserved functions.

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Acknowledgments

We thank Dr J. de Vente for his kind gift of the cGMP antiserum, Dr. M. Stern for the discussion during the preparation of the manuscript, and Nadine Seiferth for technical support. We also like to acknowledge the contribution of Susanne Giersiefer to the experiment with the ROCK inhibitor. We thank Prech Uapinyoying for reading and correcting the manuscript. M.A. Tegenge received a Georg-Christoph-Lichtenberg scholarship from the Ministry for Science and Culture of Lower Saxony. This work was supported by the BMBF grants (013925C) to E. Fritsche (013925D) to G. Bicker and DFG grant (FG 1103, BI 262/16-1).

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Authors and Affiliations

  1. Division of Cell Biology, Institute of Physiology, University of Veterinary Medicine Hannover, Bischofsholer Damm 15, 30173, Hannover, Germany

    Million Adane Tegenge & Gerd Bicker

  2. Center for Systems Neuroscience (ZSN), Hannover, Germany

    Million Adane Tegenge & Gerd Bicker

  3. Group of Molecular Toxicology, Institut für Umweltmedizinische Forschung at the Heinrich Heine-University gGmbH, Auf’m Hennekamp 50, 40225, Düsseldorf, Germany

    Thomas Dino Rockel & Ellen Fritsche

  4. Department of Dermatology, University Hospital, RWTH Aachen, Pauwelsstraûe 30, 52074, Aachen, Germany

    Ellen Fritsche

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  1. Million Adane Tegenge
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  2. Thomas Dino Rockel
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  3. Ellen Fritsche
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  4. Gerd Bicker
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Correspondence to Ellen Fritsche or Gerd Bicker.

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Tegenge, M.A., Rockel, T.D., Fritsche, E. et al. Nitric oxide stimulates human neural progenitor cell migration via cGMP-mediated signal transduction. Cell. Mol. Life Sci. 68, 2089–2099 (2011). https://doi.org/10.1007/s00018-010-0554-9

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