Human medulloblastoma cell line DEV is a potent tool to screen for factorsinfluencing differentiation of neural stem cells

The aim of our study was to investigate whether a human neural cell line co uld be used as a reliable screening tool to examine the functional conserva tion, in humans, of transcription factors involved in neuronal or glial spe cification in other species. Gain-of-function experiments were performed on DEV cells, a cell line derived from a human medulloblastoma. Genes encodin g nine different transcription factors were tested for their influence on t he process of specification of human DEV cells towards a neuronal or glial fate. In a first series of experiments, DEV cells were transfected with mur ine genes encoding transcription factors known to be involved in the neuron al differentiation cascade. Neurogenins-1, -2, and -3; Mash-1; and NeuroD i ncreased the differentiation of DEV cells towards a neuronal phenotype by a factor of 2-3.5. In a second series of experiments, we tested transcriptio n factors involved in invertebrate glial specification. In the embryonic Dr osophila CNS, the development of most glial cells depends on the master reg ulatory gene glial cell missing (gcm). Expression of gem in DEV cells induc ed a twofold increase of astrocytic and a sixfold increase of oligodendrogl ial cell types. Interestingly, expression of tramtrack69, which is required in all Drosophila glial cells, resulted in a fourfold increase of only the oligodendrocyte phenotype. Expression of the related tramtrack88 protein, which is not expressed in the fly glia, or the C. elegans lin26 protein sho wed no effect. These results show that the Drosophila transcription factor genes tested can conserve their function upon transfection into the human D EV cells, qualifying this cell line as a screening tool to analyze the mech anisms of neuronal and glial specification. J. Neurosci. Hes. 65.17-23, 200 1. (C) 2001 Wiley-Liss, Inc.