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RL Chow, B Snow, J Novak, J Looser, C Freund, D Vidgen, L Ploder, RR McInnes; The Role of Vsx1, a Rapidly Evolving Paired-like Homeodomain Transcription Factor in Mouse Eye Development and Cone Bipolar Cell Formation . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2443.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Mouse Vsx1 encodes a paired-like homeodomain (HD) transcription factor and is a member of a family of transcription factors distinguished by the presence of the CVC domain, a conserved 56 amino acid sequence C-terminal to the HD. In mammals, Chx10, a Vsx1 homologue, is essential both for the proliferation of retinal progenitor cells and for the formation or survival of retinal bipolar interneurons. Phylogenetic analysis suggests that Vsx1 and its putative vertebrate orthologues have evolved rapidly. The aim of this study is to examine the expression pattern of mouse Vsx1 and its requirement in eye development. Methods: The mouse Vsx1 expression pattern was determined using polyA-RNA blots, RT-PCR, in situ hybridization and double-immunolabeling experiments with an affinity-purified Vsx1 antibody and retinal cell type-specific antibodies. Vsx1-null mice were generated using standard gene targeting techniques. Results: Vsx1 expression was detected on multi-tissue RNA blot analysis at appreciable levels, only in the neuroretina. Vsx1 expression was first detected by in situ hybridization at post-natal day 5, solely within the outer tier of the INL region in the central neuroretina. Vsx1 expression extended all the way to the distal tip of the neuroretina in the adult. Double-immunolabeling experiments revealed that Vsx1 colocalized with antibodies to recoverin, which identify a subset of putative OFF- and ON- cone bipolar cells in the mouse. Since not all Vsx1-positive cells were labeled by recoverin, Vsx1 may also be present in recoverin-negative cone bipolar cells. Vsx1 did not colocalize with the rod bipolar cell marker PKC, nor with amacrine, horizontal or Müller's cell markers. Vsx1-null mice were generated using two different gene-targeting constructs. One construct involved a simple deletion of Vsx1 exons 1 through 4 (including the homeodomain and most of the CVC domain). The other construct replaced the endogenous Vsx1 start codon and exon 1 with a tau-LacZ fusion protein without disrupting the rest of the Vsx1 gene. Conclusion: Vsx1 is expressed predominantly in the adult mouse retina and is restricted to cone bipolar interneurons. The rapid evolution of Vsx1 orthologues is noteworthy given the divergent nature of vertebrate cone photoreceptors, which are dependent on Vsx1-expressing cone bipolar cells for signal integration and for communication with ganglion cells. Analysis of Vsx1 null mice will provide insight into the role of Vsx1 in the development of the eye and cone bipolar cells.
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