Immunology/Neurology

Malone Research Laboratory: Amy Lindgren and Minil Mikkili
de Bellard Research Laboratory: Darwin Martinez

“Epigenetic Control of Slit2 Silencing in Migratory Neural Crest Cells.”

How genes are regulated in different cell types, such as skin or bone, and turned on/off in normal development is poorly understood. The goal of this project is to isolate and characterize the DNA region that controls expression of an inhibitor of migration/motility/metastasis gene, termed Slit2, using molecular biology techniques in cells ideally suited for answering this fundamental question.

Precisely controlling when and where genes are turned on and off, known as controlling gene expression, is necessary for all cells to develop and function normally and avoid becoming cancerous or dying prematurely. This project focuses on how a gene called Slit2 is turned on and off. The Slit2 gene is a chemorepellant; that is to say Slit2 prevents cells from moving.

The development of a fertilized egg to a whole functional organism requires that cells move around to build all of the parts of an organism; this process is called cell migration. Since the Slit2 gene prevents cell migration, it is absolutely essential that it be turned on and off in a precise manner. Our goal is to study how the Slit2 gene is turned on and off in the cells that become part of the brain called the neural crest.  These cells must migrate through the embryo in order to become part of a functional brain. The availability of pre-migratory (Slit2 gene on) and migratory (Slit2 gene off) neural cells that grow in flasks of media in the laboratory makes our system ideal for studying the control of the on/off of Slit2 gene expression. Results gathered from our study will not only enhance the understanding of how this particular gene is turned on and off in normal development, but will provide clues to why the Slit2 gene is turned off in certain aggressive cancer cells that are able to then migrate away from the original tumor to form malignant metastases. Understanding the on/off control of a gene is the first step in being able to manipulate its control for therapeutic reasons.