Andrea S. Viczian, PhD
Genes and Genetic Networks Drive Neural Retina Formation
A central question in developmental biology is, ‘What genes are required for neural tissue formation?’ My lab is interested in studying the delicate, yet diligent neural tissue in the eye – the retina. Our group uses both frog (Xenopus laevis) and mouse (Mus musculus) to answer this question. By studying these very different animals, we hope to uncover evolutionarily conserved, fundamental mechanisms that drive retinal formation in all organisms.
Despite millions of years of evolution, the frog embryo grows a retina that is curiously similar to the human retina, yet the frog embryo develops outside the uterus. This makes studying eye development in frog much easier than mammalian models of human disease, like mouse (see TedX talk). In using the frog embryo, we discovered that a collection of seven transcription factors drive the formation of a functional ectopic eye. In this same study, we found a protein (Noggin) that activated the expression of the seven transcription factors, and therefore, could be used in their place. We continued to study the molecular and cellular interactions associated with these transcription factors over the next few years. We discovered that stem cells are directed to become neural cells because of the activity of Noggin (through repression of the BMP and Activin signaling pathways), and the T-box transcription factor, Tbx3. After a subset of embryonic cells are neural, another transcription factor, Pax6, becomes active in the front neural edge of the embryo and initiates a critical tipping point of genetic activity that leads to eye formation. We are further studying these factors in mouse to determine if their function is evolutionarily conserved. By studying the genes and genetic networks that lead to eye formation, we will know how these transcription factors function and how mutations in these factors could lead to blindness. Once we know the root cause of a blinding disease, future studies will allow us to determine targeted treatment options.
The mouse grows a retina that has a diversity of retinal cell types also found in the human retina. Because most eye development happens in the mouse fetus, we have developed a mouse embryonic stem cell culture system to study early retinal development in the petri dish. In this way, we can challenge our hypothesis about what we think are the early events that happen in utero and testing them in cell culture. At the same time, we have recently taken advantage of transgenic mouse models to study genes we think are involved in eye formation. We are using transgenic mice to, again, contest our idea that particular transcription factors are required for normal retina formation. The results of these studies will lead to a better understanding of eye development in a mammalian system.
Using this multi-prong approach allows us to check our hypotheses in several ways. Our recent work has yielded exciting results that have taken us in a new direction. We look forward to you joining us at this leading edge of scientific discovery. Please contact Dr. Viczian for more details.