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The Journal of Neuroscience, January 31, 2007, 27(5):973-980; doi:10.1523/JNEUROSCI.4132-06.2007

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Development/Plasticity/Repair
Stromal Cell-Derived Factor-1 Antagonizes Slit/Robo Signaling In Vivo

Sreekanth H. Chalasani,^1 * Angela Sabol,^1 * Hong Xu,¹ Michael A. Gyda,² Kendall Rasband,³ Michael Granato,² Chi-Bin Chien,³ and Jonathan A. Raper¹

¹Neuroscience Department and ²Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, and ³Department of Neurobiology and Anatomy, University of Utah Medical Center, Salt Lake City, Utah 84132

Correspondence should be addressed to Jonathan A. Raper, Neuroscience Department, University of Pennsylvania School of Medicine, 1115 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104. Email: raperj{at}mail.med.upenn.edu

Retinal ganglion cell axons exit the eye, enter the optic stalk, cross the ventral midline at the optic chiasm, and terminate in the optic tectum of the zebrafish. While in the optic stalk, they grow immediately adjacent to cells expressing the powerful retinal axon repellent slit2. The chemokine stromal cell-derived factor-1 (SDF1) is expressed within the optic stalk and its receptor CXCR4 is expressed in retinal ganglion cells. SDF1 makes cultured retinal axons less responsive to slit2. Here, we show that reducing SDF1 signaling in vivo rescues retinal axon pathfinding errors in zebrafish mutants that have a partial functional loss of the slit receptor robo2. In contrast, reducing SDF1 signaling in animals that completely lack the robo2 receptor does not rescue retinal guidance errors. These results demonstrate that endogenous levels of SDF1 antagonize the repellent effects of slit/robo signaling in vivo and that this antagonism is important during axonal pathfinding.

Key words: axon guidance; retinal ganglion cell; zebrafish; SDF-1; slit; astray; modulation

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Received Sept. 21, 2006; revised Dec. 9, 2006; accepted Dec. 16, 2006.

Correspondence should be addressed to Jonathan A. Raper, Neuroscience Department, University of Pennsylvania School of Medicine, 1115 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104. Email: raperj{at}mail.med.upenn.edu

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