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NG2-cells are not the cell of origin for murine neurofibromatosis-1 (Nf1) optic glioma

Oncogene volume 33, pages 289–299 (2014)Cite this article

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Abstract

Low-grade glial neoplasms (astrocytomas) represent one of the most common brain tumors in the pediatric population. These tumors frequently form in the optic pathway (optic pathway gliomas, OPGs), especially in children with the neurofibromatosis type 1 (NF1)-inherited tumor predisposition syndrome. To model these tumors in mice, we have previously developed several Nf1 genetically-engineered mouse strains that form optic gliomas. However, there are three distinct macroglial cell populations in the optic nerve (astrocytes, NG2+ (nerve/glial antigen 2) cells and oligodendrocytes). The presence of NG2+ cells in the optic nerve raises the intriguing possibility that these cells could be the tumor-initiating cells, as has been suggested for adult glioma. In this report, we used a combination of complementary in vitro and novel genetically-engineered mouse strains in vivo to determine whether NG2+ cells could give rise to Nf1 optic glioma. First, we show that Nf1 inactivation results in a cell-autonomous increase in glial fibrillary acidic protein+ (GFAP+), but not in NG2+, cell proliferation in vitro. Second, similar to the GFAP-Cre transgenic strain that drives Nf1 optic gliomagenesis, NG2-expressing cells also give rise to all three macroglial lineages in vivo. Third, in contrast to the GFAP-Cre strain, Nf1 gene inactivation in NG2+ cells is not sufficient for optic gliomagenesis in vivo. Collectively, these data demonstrate that NG2+ cells are not the cell of origin for mouse optic glioma, and support a model in which gliomagenesis requires Nf1 loss in specific neuroglial progenitors during embryogenesis.

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Acknowledgements

We appreciate the excellent technical assistance of Angela Petti and Belinda McMahan in the Ophthalmology Core Facility for preparing the optic nerve sections. This work was funded by a grant from the National Cancer Institute (U01-CA141549 to DHG), whereas the Ophthalmology Core Facility is funded by a grant from the National Eye Institute (EY02687).

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  1. Department of Neurology, Washington University School of Medicine, St Louis, MO, USA

    A C Solga, S M Gianino & D H Gutmann

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  1. A C Solga
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Correspondence to D H Gutmann.

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Solga, A., Gianino, S. & Gutmann, D. NG2-cells are not the cell of origin for murine neurofibromatosis-1 (Nf1) optic glioma. Oncogene 33, 289–299 (2014). https://doi.org/10.1038/onc.2012.580

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