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The Journal of Neuroscience, July 19, 2006, 26(29):7619-7628; doi:10.1523/JNEUROSCI.0855-06.2006

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Cellular/Molecular
Specification of Optic Nerve Oligodendrocyte Precursors by Retinal Ganglion Cell Axons

Limin Gao and Robert H. Miller

Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106

Correspondence should be addressed to Robert H. Miller, Department of Neurosciences, Case Western Reserve University, 2109 Adelbert Road, SOM E721, Cleveland, OH 44106. Email: rhm3{at}cwru.edu

Cell fate commitment in the developing CNS frequently depends on localized cell–cell interactions. In the avian visual system the optic nerve oligodendrocytes are derived from founder cells located at the floor of the third ventricle. Here we show that the induction of these founder cells is directly dependent on signaling from the retinal ganglion cell (RGC) axons. The appearance of oligodendrocyte precursor cells (OPCs) correlates with the projection of RGC axons, and early eye removal dramatically reduces the number of OPCs. In vitro signaling from retinal neurites induces OPCs in responsive tissue. Retinal axon induction of OPCs is dependent on sonic hedgehog (Shh) and neuregulin signaling, and the inhibition of either signal reduces OPC induction in vivo and in vitro. The dependence of OPCs on retinal axonal cues appears to be a common phenomenon, because ocular retardation (or^J) mice lacking optic nerve have dramatically reduced OPCs in the midline of the third ventricle.

Key words: oligodendrocyte precursors; optic nerve; axon induction; sonic hedgehog; neuregulin; retinal ganglion cells

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Received Feb. 24, 2006; revised June 1, 2006; accepted June 1, 2006.

Correspondence should be addressed to Robert H. Miller, Department of Neurosciences, Case Western Reserve University, 2109 Adelbert Road, SOM E721, Cleveland, OH 44106. Email: rhm3{at}cwru.edu

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