Georgetown College. Georgetown University.

By Katherine Morrissey

Dr. Elena Casey and the students in her laboratory are fascinated by frogs. Specifically, Xenopus laevis, the African claw-toed frog. They particularly like to watch frogs in the first hours of life, tracking as their eggs shift from small, bland-looking balls into embryos with identifiable eyes, tiny brains, and spinal cords.

“It’s amazing how quickly the growth occurs,” says Dr. Casey, a professor in the Biology Department at Georgetown. “Within eight hours after fertilization, the cells in certain areas are already being instructed to begin forming the nervous system. In humans, this takes a little over two weeks.”

With this research, Dr. Casey is trying to understand how nervous systems are formed, examining the intricate and carefully timed sequence of signals and responses taking place within the embryo. Dr. Casey is particularly interested in the cell growth that leads certain collections of naïve cells into those committed to be part of the central nervous system (specialization and systemization—the process in which an embryo creates its neural network).

For vertebrates including frogs and humans, this process begins with the formation of the neural plate, a flat, circular mass of cells on the dorsal side of the embryo. By the second day of development, this cluster of cells, now programmed to become the frog’s neural system, begins to roll up, transitioning from a plate-like mass to a rather familiar looking tube, soon to become the spinal cord.

What are the signals that these cells receive to make them different than the ones around them? What are the cues instructing one cell to become neural and the one alongside it be a part of the epidermis? These changes involve molecular signals, the individual cell’s response to these signals, and a carefully timed process of development. Dr. Casey explores this process by looking at a particular family of proteins known as Sox transcription factors.

She focuses on a subset of these proteins referred to as the SoxB group because they are some of the earliest genes to respond to the embryo’s signals to form a nervous system. Within the SoxB group, there are 5 proteins that emerge at different developmental stages. Dr. Casey and the members of her lab are exploring what causes the SoxB genes to turn on and off, looking to understand what controls this process. What are the instructions that come from neighboring cells? Is the process a series of chain reactions, with certain Sox proteins emerging as others turn off?

A major goal for Dr. Casey and her students is to build a knowledge base on the formation of the nervous system and early embryo development for vertebrates as a whole. From an evolutionary perspective, within the overall map of vertebrates, biologists know which species emerged earlier, and which are farther along in the evolutionary process.

While Dr. Casey is able to look at the development of a vertebrate like a frog and see the spinal cord developing, she and her students also learn by observing the embryonic development of more basal (“simpler”) species, like the sea squirt and acorn worm (see related video), which develop a neural net rather than a centralized neural system. Such evolutionary differences in embryo development give developmental biologists important insights into the important changes that lead to the evolution of mammals and human beings.

Regardless of evolutionary status, in the lab, the frog embryos come first. Because of the size of their eggs and the speed of development, frogs are easy to study and have a long history in biological research. Even before the development of more modern scientific tools, frogs were something that early biologists were able to research efficiently, leading to Hans Spemann’s famous two headed frog experiment in 1924, a Nobel Prize-winning discovery that identified the existence of an organizer within embryos. Dr. Casey feels very connected to this history and enjoys that she’s able share it with her students, along with the research itself.

The Casey lab is the largest in the Biology Department, with four graduate students, two post-doctorate researchers, and eight undergraduates all working on research. Outside of the lab, Dr. Casey currently teaches Developmental Biology and will begin teaching Developmental Neurobiology when the department’s new Neurobiology major is introduced in the spring.

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