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This review provides a synthesis that combines data from classical experimentation and recent advances in our understanding of early eye development. Emphasis is placed on the events that underlie and direct neural retina formation and lens induction. Understanding these events represents a longstanding problem in developmental biology. Early interest can be attributed to the curiosity generated by the relatively frequent occurrence of disorders such as cyclopia and anophthalmia, in which dramatic changes in eye development are readily observed. However, it was the advent of experimental embryology at the turn of the century that transformed curiosity into active investigation. Pioneered by investigators such as Spemann and Adelmann, these embryological manipulations have left a profound legacy. Questions about early eye development first addressed using tissue manipulations remain topical as we try to understand the molecular basis of this process. [ABSTRACT FROM AUTHOR]

Abstract: Chx10/Vsx2 and Vsx1 are the only Paired-like CVC (Prd-L:CVC) homeobox genes in the mouse genome. Both are expressed in the retina and have important but distinct roles in retinal development. Mutations in Chx10/Vsx2 cause reduced retinal progenitor cell (RPC) proliferation and an absence of bipolar cells, while mutations in Vsx1 impair differentiation of cone bipolar cells. Given their structural similarities and importance in retinal development, we sought to determine if a regulatory interaction exists between these genes and whether inactivation of both genes blocks initiation of retinal development. We found that Chx10/Vsx2 binds to a specific sequence in the Vsx1 5′-intergenic region and represses the activity of a luciferase reporter under the control of the Vsx1 promoter. This is consistent with our observation that there is an inverse relationship between the levels of Chx10/Vsx2 and Vsx1 immunostaining within the bipolar cell class. Furthermore, Vsx1 mRNA is upregulated in the RPCs of Chx10/Vsx2 deficient mice and zebrafish embryos injected with a chx10/vsx2 morpholino. In mice deficient for both Chx10/Vsx2 and Vsx1 and zebrafish embryos co-injected with chx10/Vsx2 and vsx1 morpholinos, the changes in embryonic retinal development and marker expression are similar in magnitude to embryos with Chx10/Vsx2 loss of function only. From these studies, we propose that Vsx1 is a direct target of Chx10/Vsx2-mediated transcriptional repression. Although Vsx1 mRNA is upregulated in Chx10/Vsx2 deficient RPCs, Vsx1 does not genetically compensate for loss of Chx10/Vsx2, demonstrating that Prd-L:CVC genes, although important, are not absolutely required to initiate retinal development. [Copyright &y& Elsevier]