HGNC Approved Gene Symbol: VAX2
Cytogenetic location: 2p13.3 Genomic coordinates (GRCh38) : 2:70,900,576-70,933,446 (from NCBI)
In connection with a project aimed at identifying human cDNAs similar to Drosophila mutant genes, Banfi et al. (1996, 1997) screened an EST database and identified more than 200 such human cDNAs, termed DRES (Drosophila-related expressed sequences). One of the DRES genes, DRES93, was found to have significant homology with the homeodomain of the Drosophila gene 'empty spiracles' (ems), which plays a major role in controlling development of the head of the fly. Two vertebrate homologs of this gene, EMX1 (600034) and EMX2 (600035), had been cloned, and they had been shown to be expressed in the developing dorsal telencephalon in Xenopus and in the developing cerebral cortex in mouse. To provide a more detailed characterization of the DRES93 cDNA, Barbieri et al. (1999) isolated the human, murine, and Xenopus full-length transcripts. Sequence analysis showed that this gene is highly similar to the VAX1 gene (604294), and it was accordingly named VAX2. By in situ hybridization, Barbieri et al. (1999) found that the VAX2 gene was almost exclusively expressed in the ventral portion of the retina during development.
To gain insight into the putative function of VAX2, Barbieri et al. (1999) injected the human and the Xenopus transcripts into Xenopus embryos to determine the phenotypic effects of its overexpression during development. The phenotype observed confirmed that VAX2 may play an important role in morphogenetic processes underlying the correct development of the eye, particularly in the establishment of a correct dorsoventral pattern.
Kim and Lemke (2006) found that Vax2 shuttled between the nucleus and cytoplasm as a function of time in the developing mouse eye, and that this dynamic shuttling was an essential feature of retinal differentiation. The subcellular localization of Vax2 was controlled by phosphorylation of ser170, downstream from its homeodomain, and this modification resulted in exclusion of Vax2 from the nucleus. Expression of a nonphosphorylatable, constitutively nuclear Vax2 in the chick optic vesicle resulted in constitutive repression of Pax6 (607108) and led to formation of an eyeless embryo.
By PCR analysis of a radiation hybrid panel, Barbieri et al. (1999) mapped the VAX2 gene to 2p13, in the vicinity of the EMX1 gene on 2p14-p13. Using genetic mapping techniques, they mapped the mouse Vax2 gene to chromosome 6, also close to the murine Emx1 gene. The authors noted that the murine Vax1 and Emx2 genes are close together on chromosome 19 in a region showing homology of synteny with human 10q25-q26, where the EMX2 gene maps. The close mapping, together with the significant degree of sequence similarity between the VAX and EMX genes, indicated that these genes may have a common origin. Barbieri et al. (1999) suggested that they may have arisen from the tandem duplication of an ancestor gene, subsequently followed by an interchromosomal duplication. It remained to be seen whether the genomic organization of the VAX and EMX genes also has an implication in terms of spatial and temporal patterns of gene expression.
The vertebrate retina and optic nerve are strikingly different in size, organization, and cellular diversity, yet the 2 structures develop from the same embryonic neuroepithelium. In mice deficient in both Vax1 and Vax2, Mui et al. (2005) found that the region normally occupied by the optic nerve was replaced by doubled-over retinal tissue that extended to the midline of the brain. They also determined that normal ventralization of the developing eye field is mediated, at least in part, by Vax repression of the Pax6 gene, a potent inducer of retinal development.
Banfi, S., Borsani, G., Bulfone, A., Ballabio, A. Drosophila-related expressed sequences. Hum. Molec. Genet. 6: 1745-1753, 1997. [PubMed: 9300667] [Full Text: https://doi.org/10.1093/hmg/6.10.1745]
Banfi, S., Borsani, G., Rossi, E., Bernard, L., Guffanti, A., Rubboli, F., Marchitiello, A., Giglio, S., Coluccia, E., Zollo, M., Zuffardi, O., Ballabio, A. Identification and mapping of human cDNAs homologous to Drosophila mutant genes through EST database searching. Nature Genet. 13: 167-174, 1996. [PubMed: 8640222] [Full Text: https://doi.org/10.1038/ng0696-167]
Barbieri, A. M., Lupo, G., Bulfone, A., Andreazzoli, M., Mariani, M., Fougerousse, F., Consalez, G. G., Borsani, G., Beckmann, J. S., Barsacchi, G., Ballabio, A., Banfi, S. A homeobox gene, vax2, controls the patterning of the eye dorsoventral axis. Proc. Nat. Acad. Sci. 96: 10729-10734, 1999. [PubMed: 10485894] [Full Text: https://doi.org/10.1073/pnas.96.19.10729]
Kim, J. W., Lemke, G. Hedgehog-regulated localization of Vax2 controls eye development. Genes Dev. 20: 2833-2847, 2006. [PubMed: 17043310] [Full Text: https://doi.org/10.1101/gad.1462706]
Mui, S. H., Kim, J. W., Lemke, G., Bertuzzi, S. Vax genes ventralize the embryonic eye. Genes Dev. 19: 1249-1259, 2005. [PubMed: 15905411] [Full Text: https://doi.org/10.1101/gad.1276605]