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Mary Beth Hatten's role in developing methods for real-time imaging of neuronal migration and research on the development of cerebellar architecture caught our attention. Curious to know more, BioTechniques contacted her to find out about the ambitions, character, and motivations that led to her success.
A New Way of Expression
What is your most significant contribution to your field?
In the 1980s, we showed that glial cells provide a template for neuronal organization and developed methods to purify granule cells and astroglia from the cerebellum. Up until that time, beautiful static images obtained by Dr. Pasko Rakic at Yale University and others indicated that neurons migrate on astroglia to form the architecture of the brain. With video microscopy techniques developed in our lab, we were able to show the active migration of neurons on the glial processes and then describe the biochemistry and ligands involved.
What led you to research neuronal migration?
I started off as a cancer biologist studying changes in membrane lipid fluidity and receptor interactions associated with metastasis and became interested in cell migration in the brain. I thought that if I could study biologically controlled migrations, I might gain a greater understanding of cancer cell migrations.
Since then, I have focused on the normal development of the cerebellum, using techniques we developed such as granule cell purification and retroviral delivery of DNA into rapidly dividing granule cells. I remain passionately interested in migration and the genes controlling granule cell development. In the early postnatal period, the granule cell cycle decreases from 24 hours to 12–14 hours, which is as fast as any rapidly growing cancer cell. We are currently studying how that remarkable expansion is controlled. As part of these studies over the last 5 years, we have established collaborations with people studying medulloblastoma—the most prominent pediatric brain tumor—which arises from granule cells. This has brought about a return to the field of cancer biology.
What is currently the most important research question in your discipline?
A great moment occurred when I first came to The Rockefeller University and was asked to present my research to the board. Following my talk, Mr. David Rockefeller, of all people, raised his hand and asked, “But why would the young neuron want to leave the place where it was born?” That question remains compelling today because brain malformations and dysfunction, including retardation, autism, and epilepsy, often involve a failure of neuronal migration. The current challenge is to understand the molecular control of this highly specialized motility.
Who had the biggest influence on your scientific career? What impact did they have on you?
Torsten Wiesel, president emeritus of The Rockefeller University, has been an important mentor to me because of his example, the quality of his science, and his friendship over the years. I was particularly influenced by his research on cortical organization and critical periods during the development of the visual system, whichprovided a beautiful example of how basic research can enable solutions to broad problems. Because of his research, surgeons realized that they had to remove cataracts in children much earlier if they were going to restore sight.
Another important influence was an amazing teacher I had in the 5th and 6th grades named Mrs. Little. She inspired me to believe that I could do anything that I wanted to do and sparked my interest in science at that early age. That confidence that I could pursue my dreams was essential.
Are you involved in volunteer work?
While at Columbia University, I pioneered a program to introduce disadvantaged kids to the laboratory, which has probably been the most rewarding volunteer work that I have done. Continuing the program at Rockefeller, I invited 5th graders into the lab and we did a simple alcohol extraction of DNA from frogs. I was not tuned in to the fact that this was the year of “Jurassic Park” until I saw one of the children about 6 months later and the tube dropped out of his pocket. He was carrying around his frog DNA because it was such a treasure to him. It was cute. But it can also be heartbreaking when conversations with students reveal the difficult challenges they face without privileges we take for granted. So it's sobering sometimes, but on the other hand very exciting to see the experiences in the lab open a new world that many of the kids never knew was available. It's like introducing them to a new way of expression, and several have gone on to choose careers in science.
