Adult spinal cord progenitor cells are repelled by netrin-1 in the embryonic and injured adult spinal cord

doi:10.1073/pnas.0703240104

Adult spinal cord progenitor cells are repelled by netrin-1 in the embryonic and injured adult spinal cord

*Department of Neurosurgery, University of Washington, Seattle, WA 98195;
^§Centre for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, QC, Canada H3A 2B4;
^†The Miami Project to Cure Paralysis and Department of Neurosurgery, University of Miami School of Medicine, Miami, FL 33101; and
^‡Genentech, San Francisco, CA 95688

Edited by Corey S. Goodman, Renovis, South San Francisco, CA, and approved September 11, 2007 (received for review May 2, 2007)

Abstract

Adult neural progenitor cells (aNPCs) exhibit limited migration in vivo with the exception of the rostral migratory stream and injury-induced movement. Surprisingly little is known regarding those signals regulating attraction or inhibition of the aNPC. These studies demonstrate that aNPCs respond principally to a repulsive cue expressed at the embryonic floor plate (FP) and also the injured adult CNS. Adult spinal cord progenitor cells (aSCPs) were seeded onto organotypic slice preparations of the intact embryonic or injured adult spinal cord. Cell migration assays combined with genetic and molecular perturbation of FP-derived migration cues or aSCP receptors establish netrin-1 (Ntn-1) but not Slit-2, Shh, or Ephrin-B3 as the primary FP-derived repellant. When slices were prepared from injured spinal cord, aSCP migration away from the injury core was Ntn-1-dependent. These studies establish Ntn-1 as a critical regulator of aSCP migration in the intact and injured CNS.

Footnotes

^¶To whom correspondence should be addressed. E-mail: phorner{at}u.washington.edu
Author contributions: A.P. and P.J.H. designed research; A.P. performed research; A.P., D.L.S., D.J.L., M.T.-L., and T.E.K. contributed new reagents/analytic tools; A.P. and P.J.H. analyzed data; and A.P., T.E.K., and P.J.H. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0703240104/DC1.
Abbreviations:

aSCP,

adult SC progenitor cell;

CM,

conditioned media;

DIV,

days in vitro;

En,

embryonic day n;

FP,

floor plate;

HEK,

human embryonic kidney cell;

KO,

knockout;

Ntn-1,

netrin-1;

NSC,

neural stem cell;

SC,

spinal cord;

VN,

ventral neuroepithelium.