Heads of Laboratories
Dr. Hatten is investigating how the complex cellular architecture of the mammalian brain is assembled during embryonic development. Exploring cell differentiation and migration, her research has broad significance for human genetic studies on brain diseases and clinical implications for conditions that are partially due to developmental abnormalities in the brain, such as learning disabilities, childhood epilepsy, schizophrenia and autism. Her work on cerebellar development also could one day inform research on treatments for childhood cancers.
Using the mouse cerebellar cortex as a model for central nervous system development, Dr. Hatten studies the mechanisms of fate specification both during the early stages of brain development and in the cellular migrations that occur in later periods. During migration, postmitotic central nervous system neurons use a system of radial glial fibers in order to direct cell movements. In live imaging studies of cerebellar granule neuron migration in vitro, the Hatten lab has revealed distinct features of glial-guided migration, including the extension of a highly polarized, leading process in the direction of migration, the assembly of an interstitial adhesion junction beneath the cell soma, localization of acto-myosin contractile motors in the proximal portion of the leading process and the formation of a perinuclear cage of tubulin to maintain the posterior positioning of the nucleus. Together, the findings suggest a model in which acto-myosin contractility in the leading process, rather than in a classical “leading edge” at the tip of the leading process, provides the force needed to “pull” the centrosome and soma forward during glial-guided migration.
Dr. Hatten has also extensively studied the neuron-glial adhesion protein astrotactin (ASTN1), a ligand she discovered in 1987. The Astn1 gene is expressed by neurons migrating along glial fibers in both the cerebellum and the cerebral cortex, and functional assays provide evidence that ASTN1 functions in neuronal migration. The lab has also characterized a second member of the ASTN family, ASTN2, which has been implicated in several common disorders of the nervous system including attention deficit hyperactivity disorder, autism and schizophrenia. Recent experiments showed that Astn2 is heavily expressed in cerebellar granule neurons when glial-guided migration is ongoing. Moreover, ASTN2 forms a complex with ASTN1 that regulates surface expression of ASTN1, and forward movement of the neuron involves the polarized trafficking of ASTN1-containing vesicles, suggesting a key role for intracellular trafficking pathways in directed migrations of neurons along glial fibers during brain development.
Members of the Hatten lab are also working to isolate new families of genes involved in migration. Dr. Hatten has collaborated with Nathaniel Heintz to create a brain “atlas” of gene expression. The project, called GENSAT (Gene Expression Nervous System Atlas), has identified several new families of genes important for migration, including some that suggest how cerebellar circuitry is formed.
Additionally, the Hatten lab is looking into the mechanisms that control the proliferation of immature cerebellar granule cells, which are important for both development and childhood cancer. In collaboration with researchers at St. Jude Children’s Research Hospital, Dr. Hatten discovered that the tumor suppressor genes Ink4c and p53 repress the formation of medulloblastoma, one of the most devastating childhood brain tumors.
Recently, her lab has also shown that embryonic stem cells implanted in the mouse brain develop into fully differentiated granule neurons. Her team is using new genetic tools to directly compare gene expression profiles of stem cells differentiated to a granule cell fate with native cells in the developing brain. The hope is that this work could lead to the design of novel methods to replace neurons in the diseased or injured brain.
Dr. Hatten graduated from Hollins College in 1971 with a bachelor’s degree in chemistry. She received her Ph.D. in biochemical sciences from Princeton University in 1975 and then did her postdoctoral research in neuroscience at Harvard Medical School. In 1978 she accepted a faculty position at New York University School of Medicine and remained there until 1987, when she moved to the College of Physicians and Surgeons at Columbia University. She came to Rockefeller in 1992 and was named the Frederick P. Rose Professor in 2000. In 2005 Dr. Hatten was Wiersma Visiting Professor of Neuroscience at the California Institute of Technology.
Dr. Hatten received the Weil Award from the American Association of Neuropathologists in 1996. In 1991 she received the McKnight Endowment Fund for Neuroscience Investigator Award, the Javits Neuroscience Investigator Award and a Faculty Award for Women Scientists and Engineers from the National Science Foundation. She also received the Pew Neuroscience Award in 1988 and the Irma T. Hirschl Fund Career Scientist Award in 1980. Dr. Hatten is a fellow of the American Association for the Advancement of Science.
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