Adult spinal cord progenitor cells are repelled by netrin-1 in the embryonic and injured adult spinal cord.
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.
Petit
Audrey
A
Department of Neurosurgery, University of Washington, Seattle, WA 98195, USA.
Sellers
Drew L
DL
Liebl
Daniel J
DJ
Tessier-Lavigne
Marc
M
Kennedy
Timothy E
TE
Horner
Philip J
PJ
D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D018920:Coculture Techniques; D004622:Embryo, Mammalian; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000494:pharmacology*; D000075388:Netrin-1; D013116:Spinal Cord / Q000196:embryology / Q000502:physiology* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000494:pharmacology*
C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D025521:Tumor Suppressor Proteins; D049452:Green Fluorescent Proteins; D000075388:Netrin-1