e start our lives as a cluster of cells, but exactly how we go from a bundle of cells to a bundle of joy remains a mystery. How do our cells know to develop into a liver cell, a brain cell, or a red blood cell? And how do our cells retain this information so that they don’t regenerate into a different type of cell altogether? Larysa Pevny, assistant professor of genetics, is working to understand both aspects of this transformation by examining the function of a subfamily of genes known as SOXB1.

Pevny studies in mice the earliest beginnings of the adult nervous system — a region of cells called the neural plate. The adult mouse nervous system, like our nervous system, is made up of neurons and glial cells. But, Pevny explains, it starts as a sheet of like cells called the epiblast. Epiblast cells receive signals that cause them to form three distinct cell layers — the ectoderm, the mesoderm, and the endoderm. Ectoderm cells eventually form skin, hair, the brain, and the nervous system.

Because these primitive cells are a blank slate waiting for the proper signal to decide their fate within the body, they are used extensively by researchers to study the process of cellular differentiation. For example, it is possible to use retinoic acid (RA), a form of vitamin A, to coax ectodermal cells into differentiating into neural cells. RA is a tool used in the lab, but what are the natural signals for this transformation in the body?

To determine if SOXB1 genes initiate neural plate formation, Pevny and collaborators took advantage of the fact that an engineered cell line known as P19 ectodermal cells differentiates into neural cells when exposed to RA in a culture dish. They asked — instead of adding RA, if you maintain expression of SOX1 (one of the three SOXB1 genes), what will the cells become? The answer is neural cells, indicating that SOX1 can predispose ectodermal cells to become neural cells.

evny has also shown that while SOXB1 expression is pervasive very early in development, it is maintained later in development predominately in neural stem cells. This loss of expression is an example of the permanent loss of genetic information that is necessary in order for our bodies to function properly. Blood cells don’t regenerate into liver cells because they eventually stop expressing genes whose protein products are necessary to make such a drastic change.

Pevny uses this permanent segregation of the SOXB1 genes to locate living neural stem cells. For example, bright green fluorescent protein (GFP) can be engineered to be expressed only in cells containing SOX2. Because SOX2 expression is mimicked by the presence of neural stem cells, these genes now mark or define living neural stem cells. GFP allows researchers to visualize the target of interest, in this case SOX2, while the mouse is alive.

Because Pevny’s work helps locate these cells, it is now possible to isolate populations of neural stem cells and examine their differentiation properties in a living system. In the future such techniques may be used in transplant studies. And, with the help of GFP, researchers can now clearly see adult neural stem cells, making it easier to study the effects of alcohol, exercise, or smoking on those cells.

Pevny and others have found that SOXB1 proteins can be used to purify mouse embryonic stem (ES) cells so they are more likely to become neural cells. ES cells have the ability to generate neurons, but when researchers differentiate ES cells in the lab, what results is a variety of cell types, including neurons. Because SOXB1 genes are expressed in neural cells, Pevny has used them to suppress the formation of other cell types. This SOXB1-assisted enrichment has resulted in cell populations that are 80 to 90 percent pure neurons. A source of pure neural cells could one day be used in transplant studies involving diseases such as Alzheimer’s and Parkinson’s.