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Development 128, 3321-3330 (2001)
© 2001 The Company of Biologists Limited

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

Yoshihiko Sugimoto2, Masahiko Taniguchi4, Takeshi Yagi5, Yoshio Akagi2, Yoshiaki Nojyo3 and Nobuaki Tamamaki1,*

1 Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501 Japan
2 Department of Ophthalmology and
3 Department of Anatomy, Fukui Medical University, Fukui 910-0063, Japan
4 Department of Biochemistry and Molecular Biology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
5 Institute for Molecular and Cellular Biology, Osaka University, Suita, Osaka 565-0871, Japan

*Author for correspondence (e-mail: tamamaki{at}mbs.med.kyoto-u.ac.jp)

Accepted May 16, 2001

Oligodendrocyte precursors are produced in restricted foci of the germinative neuroepithelium in embryo brains and migrate to their sites of function, while astrocytes are produced in a wider area in the neuroepithelium. We investigated the guidance mechanisms of glial precursor (GP) cell migration in the optic nerve. GP cell migration in newborn rat optic nerve was monitored 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 positive, while some of them with large TD-positive nuclei were NG2 negative. An in 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 the optic nerve. Co-culture experiments of the optic nerve with cell clusters expressing guidance cues revealed that the migrating GP cells in the optic 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 cells with large nuclei.

Key words: Cell migration, Glial precursor, Netrin 1, O-2A, Optic nerve, Sema3a, Rat




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© The Company of Biologists Ltd 2001