A Closer Look
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A Closer Look: A developmental biologist introduces students to research on the basic mechanisms of organ formation. --- By Terri Leith
Brenda Brizuela (foreground) works with N.C. State junior Shenice Wright (left) and Shirleen Sage (center), a St. Augustine's College sophomore participating in a summer research program. Their investigations of cell-cell interactions could lead to significant information about embryonic kidney development in humans.  (Photo by Art Latham)


ornate letter Dr. Brenda Brizuela, assistant professor in the Department of Zoology, is establishing a program of research that promises to yield important new information about the earliest stages of organ development in vertebrates. At the same time, it is giving students hands-on experience in leading-edge developmental biology.

The program uses the frog Xenopus laevis as a model system for embryonic development, as Brizuela and her students “look at cell-cell communication in a new sense,” she says. “We’re asking how interaction between cells can cause them to be organized into specific tissues and organs. The frog is ideal for looking at organ formation because you can follow development from a single cell to many cells and observe how the cells interact as organogenesis proceeds to form the swimming tadpole.”

Xenopus is a particularly good tool for developmental biological study, Brizuela explains, because of the large size and sturdiness of eggs and the development of those eggs outside the animal. “They make a good model for vertebrates,” she says, “and gastrulation studies that cannot be done in mammals can be done in this lower vertebrate model system.”

Gastrulation is a stage of embryonic development that involves cell movements and rearrangements that follow the cleavage stage (a succession of mitotic cell divisions). In frogs, gastrulation produces an embryo with three germ layers ready to undergo morphological changes to form organs.

“For an organ to form, signals must be sent between cells to organize them into structures that are functional,” Brizuela says. “Proper cell-cell interaction is essential to normal organ development, so we’re interested in how an organ is formed and how it functions and what is the role of ‘tight junctions’ in this process.”

Tight junctions, adhering junctions and gap junctions are the contact areas where cell-cell interactions occur. Brizuela and her students are studying a specific family of tight-junction proteins called claudins. “We, and others, have found that some members of the claudin family are expressed in an organ-specific, or tissue-specific manner,” says Brizuela. “In these,” she explains, “we see expression in the otic placode, where the ear will form, and we also see expression in the pronephros, or the embryonic kidney.”

This particular family of tight-junction proteins has been found to be important in various human defects, says Brizuela. “Tight-junction proteins themselves have been linked with carcinogenesis, and more recently defects in tight-junction proteins have been linked to deafness and to magnesium transport in the kidney.

“If we can learn the basic mechanisms involved in organ formation, that information can help us understand what is going on with humans,” she says. “The simple embryonic kidney in Xenopus can be used as a model to study the genesis of multicomponent organ systems, such as the human adult kidney.”

Brizuela is also interested in the role of tight-junction proteins in the development of the eye and the blood/brain barrier in the frogs and other organs where she has shown gene expression or an effect by altering protein expression.

In determining the mechanisms that allow tight junctions to affect organ formation, Brizuela has investigated what happens when cell-cell interactions are perturbed: One experiment causing an overexpression of claudins made the difference between a normal heart formation and a completely inverted heart and gall bladder. This is one among several attempts to look at important regulatory mechanisms that might be involved in how cells are dividing and where they are moving. Such efforts to delineate the steps along the formation of organs could be important in treating or determining their functions.

Brizuela mentions several possible impacts of this research: “It could advance our understanding of biological systems. Regulation of tight junctions could give us a new way of controlling disease. And a greater understanding of the role of tight junctions in organ formation and function will ultimately enhance health.”

An immediate value has come with what her students have experienced and opportunities other students will have access to, she says.

“We’ve set up an imaging facility [in south Gardner Hall] that we’ve used for doing injection experiments and the imaging of live samples. Having the live embryos makes them available for other students and classes. And the lab’s digital camera and fluorescent microscopy of frogs and fish have been of use to graduates, undergraduates and others in the department.

“It’s been valuable to the students I teach in developmental embryology. Having the lab available allows undergraduate assistants to come in and get experience in state-of-the-art developmental biology, in vitro fertilization, in situ hybridization (localization of gene expression in the embryo), and micromanipulation of embryos.

“One of our goals in the Zoology Department is to give our students more hands-on lab experience. It provides another way to learn the material for the student who learns best by seeing, feeling and manipulating — not just listening and reading.”

Brizuela also points to the value of recent developmental biology speaking and writing projects undertaken by her students — semester-long research in journals, in the lab and on the Internet, culminating in a written report and professional-quality Power Point presentations or poster presentations. One student explored the use of embryology as a tool for elementary education, while others offered talks on current-event topics such as transgenics, cloning, stem cell research and the societal and ethical impacts of such research.

Through these projects, Brizuela says, “students saw how developmental biology works in the real world. I’ve gotten a lot of fulfillment in showing students that developmental biology is relevant for everything and everyone.”


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