Azad Bonni, MD, PhD
Professor, Department of Neurobiology, Harvard Medical School
DF/HCC Program AffiliationNeuro-Oncology
Each year in the United States, 17000 new cases of primary brain tumors are diagnosed, of which the large majority are comprised of the gliomas. Progress in our understanding of the pathogenesis of gliomas has been slow in part because of the lack of clear markers of tumor initiation and progression. Although astrocytes or their precursors are thought to be the cell of origin in the most common gliomas that include the glioblastoma tumors, we are just beginning to characterize the mechanisms that regulate the proliferation and differentiation of astrocytes and their precursors in the developing central nervous system. In studies employing an in vitro cell culture system that recapitulates aspects of the development of the mammalian cerebral cortex, we found that CNTF-related cytokines impose a glial fate on cerebral cortical precursor cells by inducing their differentiation into astrocytes and inhibiting their differentiation into neurons. We also found that although CNTF activates both the JAK-STAT and Ras-MAPK signaling pathways in the precursor cells, the JAK-STAT signaling pathway selectively promotes astrocyte differentiation whereas the Ras-MAPK signaling pathway suppresses gliogenesis. It will be important to use studies of gliogenesis during normal development as a guide to determine if aberrancies in the mechanisms that regulate gliogenesis contribute to the pathogenesis of brain gliomas.
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