An essential role for Rax in retina and neuroendocrine system development

In vertebrates, the central nervous system (CNS) develops as a highly hierarchical, patterned organ with a vast diversity of neuronal and glial cell types. The vertebrate retina is developmentally a part of the CNS. Establishment of the vertebrate retina requires a series of developmental steps including specification of the anterior neural plate, evagination of the optic vesicles from the ventral forebrain, and differentiation of cells. The transcription factor RAX is a paired-type homeoprotein that plays a critical role in the eye and forebrain development of vertebrate species. Rax is initially expressed in the anterior neural region of developing mouse embryos, and later in the retina, pituitary gland, hypothalamus, and pineal gland. The targeted deletion of Rax in the mouse results in no eye formation and abnormal forebrain formation. In humans, mutations in the RAX gene lead to anophthalmia and microphthalmia. These observations indicate that RAX plays a pivotal role in the establishment of the retina. In addition, recent studies have reported that retina and pituitary gland tissues can be induced in a culture system from embryonic stem cells, using RAX expression as an indicator of neuronal progenitor cells in the induced tissue, and suggesting that the Rax gene is a key factor in neuronal regeneration. This review highlights the biological functions and molecular mechanisms of RAX in retina, pituitary, hypothalamus, and pineal gland development.