Abstract
Abstract: :
Purpose: Retinal development in vertebrates requires the formation of the anterior neural plate and the subsequent specification and differentiation of retinal cells. During eye development, the initially undifferentiated cells of the retina develop into a layered array of cell types with specific capabilities. These include the light sensitive photoreceptor cells, the bipolar interneuron cells that transmit electrical stimulus from the photoreceptor to the ganglion cells, which then transmit information from the eye to the brain. The formation of these cells types and their correct proportionality is necessary for normal eye function. Methods: The retinal homeobox gene Rx plays a critical role in vertebrate eye formation. Rx is first expressed in the anterior neural region of vertebrate embryos and later in the developing retina and ventral hypothalamus. A conserved role for Rx in eye formation has been shown in several species including fish, frogs, mice and humans. The medaka mutation eyeless is due to an insertion in the Rx3 gene and a loss of eyes in the zebrafish mutant strain chokh is caused by a mutation in the Rx3 gene. Overexpression of Rx in Xenopus embryos results in the formation of ectopic retinal tissue. In mice lacking functional Rx, eyes do not form. Finally, mutations in human Rx result in anophthalmia. This suggests that Rx has a function in the formation or proliferation of retinal progenitor cells, from which all other retinal cell types develop. However, Rx expression is not limited to the retinal progenitor cells. Some differentiating retinal cells express Rx for several days. Therefore, Rx might also have a function in the specification, differentiation or survival of retinal cell types. Results/Conclusions:We have utilized transgenic fish, frogs and mice as well as conditional knock–outs in mice to study the function of Rx both in retinal formation and retinal differentiation. We have also explored the evolutionary conservation of Rx between several species using promoter analysis in transgenic animals. These Rx promoter constructs have been used in gain of function experiments to analyze other genes thought to be involved in retinal formation and differentiation.
Keywords: retinal development • transcription factors • transgenics/knock-outs