Metabolic and Molecular Axes in Neuronal Differentiation

Grant Winners

Deans

Abstract

What are the specific effects of cellular metabolism that define neuronal cell fate and what are the underlying signaling cascades. These are some of the questions that will be investigated during the course of the proposed work. Low oxygen concentrations (hypoxia) occur in several physiological and pathological cellular situations such as embryogenesis and stem cell proliferation. Any changes in this redox status can mediate changes in the neuronal developmental trajectory. The mechanism through which such changes occur in the neuronal development and neuronal stem cell differentiation is still unknown. This is highly important especially since the environmental factors including exposure to pesticides and insecticides as well as alcohol and other drugs can lead to altered redox status and induce oxidative stress, eventually leading to altered neuronal development and skewed developmental trajectory. We will manipulate the redox status and investigate the effects on neuronal differentiation. We will also investigate the changes in underlying gene expression that could contribute to changes in the neuronal fate and neuronal differentiation. Autophagy is a process that controls such oxidative stress that are highly critical for the differentiation of stem cells into different types of cells. Since our previous studies report that redox status is altered in neuronal differentiation, here we will measure the effects of such altered redox status on autophagy status during neuronal differentiation. We hypothesize that autophagy and gene expression changes under the influence of altered redox status are one such mechanism to alter the neuronal development. While the short term goal is to identify the effects of altered redox status on the altered autophagy status in neuronal stem cells; the long term goal is to identify functional gene pathways that contribute to defining neuronal cell fate under the influence of redox status. Such functional pathways could contribute to neurodevelopmental disease and could be used as target to treat neurodevelopmental disorders.