A Novel Zebrafish Model of Diffuse Midline Glioma
Diffuse midline glioma (DMG), previously defined as diffuse intrinsic pontine glioma (DIPG), is an aggressive brain cancer that appears in children between 4-9 years of age. Only a few hundred children are diagnosed with DIPG/DMG in the US each year, and it is still poorly understood. There is no cure for DIPG/DMG, and children do not live more than 1-2 years after diagnosis. DIPG/DMG is a formidable type of cancer because there are no good treatment options, and it is universally lethal. Tumors may start with only a few cells very early during embryonic development, so in humans, that may be years before the cancer is diagnosed. Once these young children present with symptoms, such as coordination problems or dizziness, it is too late, as this highly aggressive cancer has already spread in the brain and surrounding tissues. Current animal models to study this cancer use genetically modified mice or mice that receive transplanted tumor cells. These models do not allow tracking and direct visualization of the tumor from its earliest stages.
Project Goals
Our objective is to develop a DIPG/DMG animal model to reveal the earliest stages of tumor development and dissect the mechanisms of tumor initiation. Specifically, we will use zebrafish to develop a model of DIPG/DMG because their genes and brain anatomy is very similar to humans, and they are very easy to work with in the lab. In Aim 1, we will define the molecular mechanisms inside early glial cells in the brain called oligodendrocyte precursor cells that transform from normal cells into cancer cells. In Aim 2, we will determine how these invasive tumor cells spread throughout the brain and into surrounding tissues. Zebrafish embryos and juveniles are mostly transparent, meaning we can look directly inside the animal when the tumor isforming. We will use different imaging approaches to detect the first tumor cells in the central nervous system. Ultimately, we hope our zebrafish model of DIPG/DMG will expand our basic understanding of these tumors, reveal potential markers for early detection, and allow screening of novel therapeuticsfor treatment.
