development of NG2 neural progenitors requires olig gene function

Development of NG2 neural progenitors requires olig gene function

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Development of NG2 neural progenitor cells requires Olig gene function Keith L. Ligon* †‡ , Santosh Kesari §¶ , Masaaki Kitada*, Tao Sun*, Heather A. Arnett § , John A. Alberta § , David J. Anderson i , Charles D. Stiles § , and David H. Rowitch* Departments of *Pediatric Oncology and § Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115; Departments of Pathology and Neurology, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115; and i Division of Biology, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125 Edited by Gerald D. Fischbach, Columbia University College of Physicians and Surgeons, New York, NY, and approved April 10, 2006 (received for review December 20, 2005) In the adult central nervous system, two distinct populations of glial cells expressing the chondroitin sulfate proteoglycan NG2 have been described: bipolar progenitor cells and more differen- tiated ‘‘synantocytes.’’ These cells have diverse neurological func- tions, including critical roles in synaptic transmission, repair, and regeneration. Despite their potential importance, the genetic fac- tors that regulate NG2 cell development are poorly understood, and the relationship of synantocytes to the oligodendroglial lin- eage, in particular, remains controversial. Here, we show that > 90% of embryonic and adult NG2 cells express Olig2, a basic helix–loop–helix transcription factor required for oligodendrocyte lineage speciFcation. Analysis of mice lacking Olig function dem- onstrates a failure of NG2 cell development at embryonic and perinatal stages that can be rescued by addition of a transgene containing the human OLIG2 locus. These Fndings show a general requirement for Olig function in NG2 cell development and high- light further roles for Olig transcription factors in neural progenitor cells. Cspg4 u oligodendrocyte u synantocyte u glia u regeneration N G2 cells are central nervous system (CNS) glial cells defined by their expression of the chondroitin sulfate proteoglycan, NG2, which is also known as Cspg4 or AN2 (1–4). A significant proportion of NG2 cells actively proliferate and indeed have been characterized as the most prevalent cycling progenitor cell population in the adult CNS (5, 6). NG2 cells have diverse functions and participate in oligodendrogenesis (7) and neuro- genesis (8), as well as the physiologic support of neurons and synaptic signaling (4, 9). They have also been proposed to play critical roles in brain repair and regeneration and are the primary responding neural cell type to CNS injury (10, 11). Despite their abundance as a progenitor population and potential importance in maintenance and repair of neurological function, the developmental ontogeny of NG2 cells remains controversial (4, 7, 12). Cytologically, they are reportedly a heterogeneous population, and two distinctive cellular morphol- ogies have been described: bipolar progenitor cells that resemble
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Development of NG2 neural progenitors requires olig gene function

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