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Monica Vetter

Professor of Neurobiology and Anatomy

B.S. McGill University, Canada

Ph.D. University of California, San Francisco

Research

References

monica @ neuro.utah.edu

Monica Vetter's Lab Page

Research

The nervous system is comprised of an astounding collection of distinct cell types, which must be generated at the appropriate place and time and in correct numbers during development. How are these cell fate decisions controlled? The retina is one of the most accessible parts of the central nervous system and has served as a wonderful model for addressing how cell fate is determined. We are using both Xenopus laevis and mouse to define at a molecular level the essential steps in the life of a progenitor cell as it progresses towards a specific retinal neuron fate.

An important theme of our work is to understand the interplay between transcription factors that regulate neural differentiation in the retina and extrinsic signaling pathways that modulate their expression or function, resulting in changes in gene expression and thus in cell fate. For example, we have been investigating the mechanisms by which proneural transcription factors promote retinal neuron differentiation, and how they contribute to the ordered sequence of retinal histogenesis. We find that both the expression and activity of these factors are controlled multiple signaling pathways. For example, we recently showed that Wnt signaling through the Fz5 receptor regulates the expression of Sox2, which is required for neural competence and the expression of proneural factors in the developing eye. Ultimately, the goal is to reveal general principles governing the development of neural stem cells and progenitors, which may inform efforts to harness these cells for the treatment of disease and injury of the nervous system.

In that vein, we have also begun to investigate the mechanisms underlying a devastating degenerative disease of the retina, namely glaucoma, which is characterized by progressive loss of retinal ganglion cells (RGCs) leading to blindness. We are focusing our efforts on understanding the changes that take place at early stages of disease using a mouse model. We find that glaucoma shares many of the hallmark features of other neurodegenerative diseases, including significant involvement of microglia. We have also found significant down-regulation of key regulatory genes within RGCs themselves, and are determining how their loss contributes to changes in the viability of RGCs. Because of these common features, glaucoma may offer a tractable system for understanding how neural tissue responds to stress or injury and degenerates over time.

A lateral view of a transgenic Xenopus embryo expressing green fluorescent protein (GFP) under the control of the Xath5 promoter. The promoter drives GFP expression selectively in the developing eye, olfactory placodes (olf) and pineal, which precisely reflects where the endogenous Xath5 gene is expressed. We are using the transgenic method to define the regulatory elements required for this tissue-specific expression.

 

References