title: The homeodomain protein Vax2 patterns the dorsoventral and nasotemporal axes of the eye.
abstract: The vertebrate retina is highly ordered along both its dorsoventral (DV) and nasotemporal (NT) axes, and this order is topographically maintained in its axonal connections to the superior colliculus of the midbrain. Although the graded axon guidance cues that mediate the topographic mapping of retinocollicular connections are increasingly well understood, the transcriptional regulators that set the DV and NT gradients of these cues are not. We now provide genetic evidence that Vax2, a homeodomain protein expressed in the ventral retina, is one such regulator. We demonstrate that in Vax2 mutant mice, retinocollicular projections from the ventral temporal retina are dorsalized relative to wild type. Remarkably, however, this dorsalization becomes systematically less severe in progressively more nasal regions of the ventral retina. Vax2 mutants also exhibit flattened DV and NT gradients of the EphA5, EphB2, EphB3, ephrin-B1 and ephrin-B2 axon guidance cues. Together, these data identify Vax2 as a fundamental regulator of axial polarization in the mammalian retina.
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, CA 92037 USA.
authors.forename: Stina H
authors.initials: SH
authors.lastname: Mui
authors.forename: Robert
authors.initials: R
authors.lastname: Hindges
authors.forename: Dennis D M
authors.initials: DD
authors.lastname: O'Leary
authors.forename: Greg
authors.initials: G
authors.lastname: Lemke
authors.forename: Stefano
authors.initials: S
authors.lastname: Bertuzzi
mesh_terms: D000818:Animals; D001369:Axons; D019521:Body Patterning; D002450:Cell Communication; D005123:Eye / Q000196:embryology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008954:Models, Biological; D009024:Morphogenesis; D012160:Retina / Q000166:cytology*; D012165:Retinal Ganglion Cells / Q000166:cytology; D013477:Superior Colliculi / Q000166:cytology*; D014018:Tissue Distribution
chemical_list: D018398:Homeodomain Proteins; C120595:Vax2 protein, mouse