Descriptor of Research
Using NF1 as an experimental platform, I have designed a system to study how maternal environmental exposures, including exposure to a high-fat, high-sucrose diet, affect specific mutant neural stem cell populations to increase pediatric glioma penetrance. My current avenues of investigation include determining whether gestational weight gain or maternal obesity impact Nf1-mutant neural stem cell (NSC) populations in the hypothalamus (third ventricular zone; TVZ) to increase optic pathway glioma incidence in mice. I have identified that maternal diet-induced obesity (DIO) increases the proliferation and glial differentiation of TVZ NSCs in both wild-type and Nf1-mutant offspring. I have further identified that this is associated with increased circulating insulin and leptin, which stimulate proliferation in isolated TVZ NSCs. I am also interested in determining how maternal DIO affects nutrient
availability in the fetal brain, and whether altered nutrient availability may underlie differences in NSC phenotype.