Netrin-1 is a chemorepellent for oligodendrocyte precursor cells in the embryonic spinal cord.
Netrin-1, secreted by floor plate cells, orients axon extension in relation to the ventral midline of the embryonic spinal cord. Oligodendrocyte precursor (OP) cells are born close to the ventral midline and migrate away from the floor plate. Here we show that OP cells, identified by expression of the platelet-derived growth factor alpha receptor, express the netrin receptors dcc and unc5h1 but do not express netrin-1. Using a microchemotaxis assay, we demonstrate that migrating OPs are repelled by a gradient of netrin-1 in vitro. Furthermore, application of netrin-1 to OPs in vitro triggers retraction of OP processes. In the absence of netrin-1 or Deleted in Colorectal Cancer (DCC) function in vivo, fewer OP cells migrate from the ventral to the dorsal embryonic spinal cord, consistent with netrin-1 acting as a repellent. In addition to their role regulating cell movement, DCC and UNC-5 homologs have been suggested to function as proapoptotic dependence receptors, triggering cell death in the absence of netrin-1. In contrast, we report no evidence of increased OP cell death in vivo or in vitro in the absence of either netrin-1 or DCC. These findings indicate that netrin-1 is a repellent cue for migrating OPs in the embryonic spinal cord.
Centre for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4.
Andrew A
AA
Jarjour
Colleen
C
Manitt
Simon W
SW
Moore
Katherine M
KM
Thompson
Sung-Joo
SJ
Yuh
Timothy E
TE
Kennedy
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000494:pharmacology / Q000502:physiology*; D000075389:DCC Receptor; D015194:Diffusion Chambers, Culture; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D000075386:Netrin Receptors; D000075388:Netrin-1; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics
D000906:Antibodies; D015815:Cell Adhesion Molecules; D002630:Chemotactic Factors; D000075389:DCC Receptor; C501910:Dcc protein, mouse; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; C000617353:Ntn1 protein, mouse; C000617354:Ntn1 protein, rat; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C000617308:Unc5A protein, mouse; D000075388:Netrin-1