Guidance of glial precursor cell migration by secreted cues in the developing optic nerve

Oligodendrocyte precursors are produced in restricted foci of the germinati ve neuroepithelium in embryo brains and migrate to their sites of function, while astrocytes are produced in a wider area in the neuroepithelium. We i nvestigated the guidance mechanisms of glial precursor (GP) cell migration in the optic nerve. GP cell migration in newborn rat optic nerve was monito red by the UV-thymine-dimer (TD) method. A double labeling study using NG2 and TD revealed that many of these in vivo migrating cells were NG2 positiv e, while some of them with large TD-positive nuclei were NG2 negative. An i n vitro cell migration study using optic nerve with chiasma and/or eyeball tissue revealed that the GP cells migrated under the guidance of repulsive cues secreted from the optic chiasma. We detected the expression of netrin 1 and Sema3a in the optic chiasma, and that of Unc5h1 and neuropilin 1 in t he optic nerve. Co-culture experiments of the optic nerve with cell cluster s expressing guidance cues revealed that the migrating GP cells in the opti c nerve were heterogeneous. Netrin 1 repelled a subtype of NG2-positive and PLP-positive GP cells with small nuclei. Sema3a repelled a subtype of GP c ells with large nuclei.