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doi: 10.1242/10.1242/dev.00326
1 Department of Medicine, University of Massachusetts Medical School, 364
Plantation Street, Worcester, MA 01605, USA
2 Department of Anatomy and Cell Biology, The Hebrew University-Hadassah Medical
School, PO Box 12272, Jerusalem 91120, Israel
3 Institut de la Santé et de le Recherche Médicale U106,
Bâtiment de Pédiatrie, Hôpital de la
Salpêtrière, 47 Boulevard de I'Hôpital, 75013, Paris,
France
4 Department of Anatomy and Neurobiology, Washington University School of
Medicine, Box 8108, 660 S. Euclid Avenue, St Louis, MO 63110, USA
5 Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston,
MA 02115, USA
* Author for correspondence (e-mail: zheng.bao{at}umassmed.edu)
Accepted 6 December 2002
Although multiple axon guidance cues have been discovered in recent years, little is known about the mechanism by which the spatiotemporal expression patterns of the axon guidance cues are regulated in vertebrates. We report that a homeobox gene Irx4 is expressed in a pattern similar to that of Slit1 in the chicken retina. Overexpression of Irx4 led to specific downregulation of Slit1 expression, whereas inhibition of Irx4 activity by a dominant negative mutant led to induction of Slit1 expression, indicating that Irx4 is a crucial regulator of Slit1 expression in the retina. In addition, by examining axonal behavior in the retinas with overexpression of Irx4 and using several in vivo assays to test the effect of Slit1, we found that Slit1 acts positively to guide the retinal axons inside the optic fiber layer (OFL). We further show that the regulation of Slit1 expression by Irx4 is important for providing intermediate targets for retinal axons during their growth within the retina.
Key words: Irx4, Slit1, Retinal axon, Expression regulation, chick
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