Wnt-Ryk signalling mediates medial-lateral retinotectal topographic mapping.
Computational modelling has suggested that at least two counteracting forces are required for establishing topographic maps. Ephrin-family proteins are required for both anterior-posterior and medial-lateral topographic mapping, but the opposing forces have not been well characterized. Wnt-family proteins are recently discovered axon guidance cues. We find that Wnt3 is expressed in a medial-lateral decreasing gradient in chick optic tectum and mouse superior colliculus. Retinal ganglion cell (RGC) axons from different dorsal-ventral positions showed graded and biphasic response to Wnt3 in a concentration-dependent manner. Wnt3 repulsion is mediated by Ryk, expressed in a ventral-to-dorsal decreasing gradient, whereas attraction of dorsal axons at lower Wnt3 concentrations is mediated by Frizzled(s). Overexpression of Wnt3 in the lateral tectum repelled the termination zones of dorsal RGC axons in vivo. Expression of a dominant-negative Ryk in dorsal RGC axons caused a medial shift of the termination zones, promoting medially directed interstitial branches and eliminating laterally directed branches. Therefore, a classical morphogen, Wnt3, acting as an axon guidance molecule, plays a role in retinotectal mapping along the medial-lateral axis, counterbalancing the medial-directed EphrinB1-EphB activity.
Schmitt
Adam M
AM
Department of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, Illinois 60637, USA.
Shi
Jun
J
Wolf
Alex M
AM
Lu
Chin-Chun
CC
King
Leslie A
LA
Zou
Yimin
Y
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002642:Chick Embryo; D051157:Frizzled Receptors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant / Q000235:genetics; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D036081:Receptors, Eph Family / Q000235:genetics / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060508:Wnt3 Protein
D051157:Frizzled Receptors; D012333:RNA, Messenger; D051153:Wnt Proteins; D060508:Wnt3 Protein; C555508:Wnt3 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D036081:Receptors, Eph Family; C118148:Ryk protein, mouse