The homeodomain protein Vax2 patterns the dorsoventral and nasotemporal axes of the eye

Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, CA 92037 USA.
Development (Impact Factor: 6.46). 03/2002; 129(3):797-804.
Source: PubMed


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.

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    • "The most ventral domain of the developing retina is characterized by early expression of Vax, ALDH3/ALDH6, Bmp7, eph-B1, -B2, -B3, RA, Pax2, Raldh3/6, and Shh in the optic cup's tissue. Vax2 may function as a global " ventralizing " regulator of the developing eye (Mic et al., 2004; Morcillo et al., 2006; Mui et al., 2002; Peters and Cepko, 2002; Ross et al., 2000; Sasagawa et al., 2002; Schulte et al., 1999; Schwarz et al., 2000; Torres et al., 1996). "
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    ABSTRACT: How the neural retina is held in its place in the human physiological living body) Bratislava 2014 Original self-publishing first edition of the monograph, entitled " Gergely's retinal linkage (How the neural retina is held in its place in the human physiological living body) " by Gergely K (contact:; affiliation: Faculty of Medicine in Bratislava, Comenius University in Bratislava, Slovak Republic; This work may not be translated or copied in whole or in part without the written permission of the publisher Květoslava Gergelyova, MD; Prague, Czech Republic (contact:, except for brief excerpts in connection with scientific articles or scholarly analysis [regular citation: Gergely K. Gergely's retinal linkage (How the neural retina is held in its place in the human physiological living body). Publisher Gergelyova, 2014]. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights.
    1. 12/2014; Gergelyova Kvetoslava,, ISBN: 978-80-260-6819-8
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    • "Vax1 homozygous null mice had colobomas detectable from the earliest stages of development that were fully penetrant and moderately severe [Hallonet et al., 1998; Bertuzzi et al., 1999]. Colobomas were rare and milder in Vax2 homozygous null mutants, but Vax1 and Vax2 double mutant mice had severe colobomas that were fully penetrant [Barbieri et al., 2002; Mui et al., 2002]. In Danio rerio, injections of antisense morpholinos against Vax1 or Vax2 results in colobomas and reduced retinal pigment at the site of the choroid fissure [Take-uchi et al., 2003]. "
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    ABSTRACT: Vax1 and Vax2 have been implicated in eye development and the closure of the choroid fissure in mice and zebrafish. We sequenced the coding exons of VAX1 and VAX2 in 70 patients with anophthalmia/microphthalmia (A/M). In VAX1, we observed homozygosity for two successive nucleotide substitutions c.453G>A and c.454C>A, predicting p.Arg152Ser, in a proband of Egyptian origin with microphthalmia, small optic nerves, cleft lip/palate, and corpus callosum agenesis. This mutation affects an invariant residue in the homeodomain of VAX1 and was absent from 96 Egyptian controls. It is likely that the mutation results in a loss of function, as the mutation results in a phenotype similar to the Vax1 homozygous null mouse. We did not identify any mutations in VAX2. This is the first description of a phenotype associated with a VAX1 mutation in humans and establishes VAX1 as a new causative gene for A/M.
    Human Mutation 02/2012; 33(2):364-8. DOI:10.1002/humu.21658 · 5.14 Impact Factor
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    • "BMP4, a TGF-Beta closely related to Dpp, has been implicated in development of progenitor cells in the dorsal half of the eye and in establishment of the DV axis of the retina in Xenopus (Papalopulu and Kintner, 1996). The dorsal selectors of the vertebrate eye, BMP-4 and TbX5, act to restrict the expression of Vax2 and Pax2 to the ventral domain of the eye (Koshiba- Takeuchi et al., 2000; Mui et al., 2002; Peters, 2002; Peters and Cepko, 2002). These DV expression domains correspond to the developmental compartments (Peters, 2002; Peters and Cepko, 2002). "
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    ABSTRACT: During organogenesis in all multi-cellular organisms, axial patterning is required to transform a single layer organ primordium into a three-dimensional organ. The Drosophila eye model serves as an excellent model to study axial patterning. Dorso-ventral (DV) axis determination is the first lineage restriction event during axial patterning of the Drosophila eye. The early Drosophila eye primordium has a default ventral fate, and the dorsal eye fate is established by onset of dorsal selector gene pannier (pnr) expression in a group of cells on the dorsal eye margin. The boundary between dorsal and ventral compartments called the equator is the site for Notch (N) activation, which triggers cell proliferation and differentiation. This review will focus on (1) chronology of events during DV axis determination; (2) how early division of eye into dorsal and ventral compartments contributes towards the growth and patterning of the fly retina, and (3) functions of DV patterning genes.
    Developmental Dynamics 01/2012; 241(1):69-84. DOI:10.1002/dvdy.22764 · 2.38 Impact Factor
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