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The Journal of Neuroscience, July 30, 2008, 28(31):7900-7910; doi:10.1523/JNEUROSCI.0617-08.2008

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Cellular/Molecular
Zebrafish Olfactomedin 1 Regulates Retinal Axon Elongation In Vivo and Is a Modulator of Wnt Signaling Pathway

Naoki Nakaya,¹ Hee-Sheung Lee,¹ Yuichiro Takada,² Itai Tzchori,³ and Stanislav I. Tomarev¹

¹Section of Molecular Mechanisms of Glaucoma, Laboratory of Molecular and Developmental Biology, National Eye Institute, ²Section for Translational Research in Retinal and Macular Degeneration, National Institute on Deafness and Other Communication Disorders, and ³National Institute of Child Health and Development, National Institutes of Health, Bethesda, Maryland 20892

Correspondence should be addressed to Stanislav Tomarev, National Eye Institute, National Institutes of Health, Building 7, Room 103, 7 Memorial Drive, MSC 0704, Bethesda, MD 20892-0704. Email: tomarevs{at}nei.nih.gov

Olfactomedin 1 (Olfm1) is a secreted glycoprotein belonging to a family of olfactomedin domain-containing proteins. It is involved in the regulation of neural crest production in chicken and promotes neuronal differentiation in Xenopus. Here, we investigate the functions of Olfm1 in zebrafish eye development. Overexpression of full-length Olfm1, and especially its BMY form lacking the olfactomedin domain, increased the thickness of the optic nerve and produced a more extended projection field in the optic tectum compared with control embryos. In contrast, injection of olfm1–morpholino oligonucleotide (Olfm1–MO) reduced the eye size, inhibited optic nerve extension, and increased the number of apoptotic cells in the retinal ganglion cell and inner nuclear layers. Overexpression of full-length Olfm1 increased the lateral separation of the expression domains of eye-field markers, rx3 and six3. The Olfm1–MO had the opposite effect. These data suggest that zebrafish Olfm1 may play roles in the early eye determination, differentiation, optic nerve extension, and branching of the retinal ganglion cell axon terminals, with the N-terminal region of Olfm1 being critical for these effects. Injection of RNA encoding WIF-1, a secreted inhibitor of Wnt signaling, caused changes in the expression pattern of rx3 similar to those observed after Olfm1–MO injection. Simultaneous overexpression of WIF-1 and Olfm1 abolished the WIF-1 effect. Physical interaction of WIF-1 and Olfm1 was demonstrated by coimmunoprecipitation experiments. We concluded that Olfm1 serves as a modulator of Wnt signaling.

Key words: eye development; axonal extension; neuronal differentiation; Wnt signaling; WIF-1; morpholino oligonucleotides

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Received Feb. 11, 2008; revised May 23, 2008; accepted June 18, 2008.

Correspondence should be addressed to Stanislav Tomarev, National Eye Institute, National Institutes of Health, Building 7, Room 103, 7 Memorial Drive, MSC 0704, Bethesda, MD 20892-0704. Email: tomarevs{at}nei.nih.gov

This article has been cited by other articles:

				H.-S. Kwon, H.-S. Lee, Y. Ji, J. S. Rubin, and S. I. Tomarev Myocilin Is a Modulator of Wnt Signaling Mol. Cell. Biol., April 15, 2009; 29(8): 2139 - 2154. [Abstract] [Full Text] [PDF]

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