Expression of Crx in the human retina. Retinopathy is caused by impaired Crx. rax induces glia cell fate

Outline The function of "seeing" comprises a process in which external light coming through the ocular lens reaches the retina, which serves as a screen, and the resulting signal is transferred through optic nerves to the brain. Retinal photoreceptor cells represent the only light sensor in mammals. Once lost, their function is never restored spontaneously. In addition, much remains unknown as to the developmental process of the retina. With the recent trends toward general population aging, the incidence of diseases accompanied by retinal degeneration, such as blindness due to diabetic complications and visual field limitation due to glaucoma, has increased, posing a serious social problem. At present, the retina cannot be reproduced by medical treatment. In the treatment of retinopathies, including those of hereditary origin, we are able to do nothing more than delaying the progression of the disease. It is expected that advances in research into retinal development will provide clues to the restoration of vision in patients suffering from such diseases. At this department, we are conducting on-going research to investigate some genes believed to play key roles in the development of the retina. The mechanisms of the cell fate determination of the central nervous system (differentiation into two kinds of nerve cells: neurons and glias) are being investigated at the molecular level. Our studies of the retina, a small organ of central nervous origin, have provided useful data that may lead to the elucidation of the mechanisms of the development of the brain, a much more complex organ consisting of several hundred billions of neurons. To lay the groundwork for future research activities, we are working on various research projects that focus on particular chemical substances that serve as signal transmitters in the brain. For example, dopamine and serotonin function in different types of neurons in the brain, and are profoundly involved in the pathology of psychiatric diseases, depression, etc. Seeking potential therapies for psychiatric and nervous diseases, we will investigate the mechanism behind the specificity for these chemical substances in brain development to enhance our understanding of these diseases. Research Activities Our vision is essential to our lives, and the loss of vision severely affects our daily activities. The retina is a membranous tissue that forms the innermost portion of the eyeball. It serves as a receptor of optical stimuli where an image is thrown by external light. Being the only light sensor in mammals, retinal photoreceptor cells have long been studied extensively by many researchers. However, the molecular mechanisms behind the development of the retina are poorly understood. At this department, we have isolated rax, Crx, and vax2, genes which play key roles in retinal development, and have made efforts to analyze their functions in an attempt to elucidate the molecular mechanisms behind the differentiation of undifferentiated retinal precursor cells to photoreceptor cells. It is expected that understanding of the retinal development, an important problem in neural biology, will be thus progressed. We will attempt to artificially induce photoreceptor cells from undifferentiated nerve precursor cells and ES cells, so as to enable the treatment of blindness in future. We will also attempt to proceed to analyzing higher visual functions, including the molecular mechanisms of the formation of our sense of color and stereoscopic vision. In addition to the retina, we will attempt to elucidate the mechanism of the determination of the fate of neurons cells in the brain and have already commenced with a new project to clarify the determination of neurotransmitter specificity in neurons. As exemplified by the relationship of Parkinson's disease or schizophrenia and dopamine neurons, and of depression and serotonin neurons, psychiatric/nervous diseases have been shown to be associated with particular neurotransmitter-specific neurons. By enhancing the understanding of the developmental processes of such neurons, we will seek possibilities for the treatment of currently difficult-to-treat psychiatric/neurological disorders. Research Subjects Mechanism of the determination of the cell fate of retinal photoreceptor cells. Mechanism of the determination of the cell fate of neurons and glias. Molecular mechanism of the determination of neurotransmitter specificity in neurons.