Netrin 1 mediates spinal cord oligodendrocyte precursor dispersal.
In spinal cord, oligodendrocyte precursors that give rise to myelin-forming cells originate in a restricted domain of the ventral ventricular zone. During development, these cells migrate widely throughout the spinal cord. Netrin 1 is expressed at the ventral ventricular zone during oligodendrocyte precursors emigration, and, in vitro, netrin 1 acts as chemorepellent and antagonizes platelet-derived growth factor (PDGF) chemoattraction. Oligodendrocyte precursors express the netrin receptors DCC and UNC5 and function-blocking anti-DCC antibody inhibits chemorepulsion of ventral spinal cord explants and netrin-secreting cells. In spinal cord slice preparations, addition of function-blocking anti-DCC antibody or netrin 1 dramatically inhibits oligodendrocyte precursor migration from the ventral ventricular zone. These data indicate the initial dispersal of oligodendrocyte precursors from their localized origin is guided by a chemorepellent response to netrin 1.
Tsai
Hui-Hsin
HH
Department of Neurosciences, Case Western Reserve University, School Of Medicine, Cleveland, OH 44106, USA.
Tessier-Lavigne
Marc
M
Miller
Robert H
RH
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D002630:Chemotactic Factors / Q000378:metabolism; D002633:Chemotaxis / Q000502:physiology*; D002642:Chick Embryo; D000075389:DCC Receptor; D006801:Humans; D066298:In Vitro Techniques; D009414:Nerve Growth Factors / Q000378:metabolism*; D000075386:Netrin Receptors; D000075388:Netrin-1; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D015815:Cell Adhesion Molecules; D002630:Chemotactic Factors; D000075389:DCC Receptor; C501909:DCC protein, human; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; C000617354:Ntn1 protein, rat; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1