Cellular and Molecular Life Sciences

, Volume 68, Issue 12, pp 2089–2099 | Cite as

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

  • Million Adane Tegenge
  • Thomas Dino Rockel
  • Ellen Fritsche
  • Gerd Bicker
Research Article


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.


Brain development Neurospheres Stem cells Cell motility Protein kinase G 



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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Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  1. 1.Division of Cell Biology, Institute of PhysiologyUniversity of Veterinary Medicine HannoverHannoverGermany
  2. 2.Center for Systems Neuroscience (ZSN)HannoverGermany
  3. 3.Group of Molecular ToxicologyInstitut für Umweltmedizinische Forschung at the Heinrich Heine-University gGmbHDüsseldorfGermany
  4. 4.Department of DermatologyUniversity HospitalAachenGermany

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