Irx4-mediated regulation of Slit1 expression contributes to the definition of early axonal paths inside the retina.
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.
Jin
Zhe
Z
Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
Zhang
Jinhua
J
Klar
Avihu
A
Chédotal
Alain
A
Rao
Yi
Y
Cepko
Constance L
CL
Bao
Zheng-Zheng
ZZ
D000818:Animals; D030161:Avian Proteins; D001369:Axons / Q000378:metabolism*; D002642:Chick Embryo; D004627:Embryonic Induction / Q000502:physiology; D005455:Fluorescent Antibody Technique; D018398:Homeodomain Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*
D030161:Avian Proteins; D018398:Homeodomain Proteins; C117570:Irx4 protein, Gallus gallus; C485534:Irx4 protein, mouse; D009419:Nerve Tissue Proteins