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Chunk #3 — 3. Induced neuronal cells — 3.1. The beginning: induced neuronal cells from developmentally related cells

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Induced neuronal reprogramming.
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neurogenesis. However, conclusions should be made cautiously when marker expression alone is used as the only criterion to define a neuron. In fact, it was later shown that neurons derived from Pax6, Mash1 and Ngn2 transduced astroglial precursors do not have any spontaneous synaptic events in the absence of cortical neurons and are therefore not fully functional. Given that neurons devoid of any synaptic events might be suggestive of an absence of a functional presynaptic and/or postsynaptic compartment, the authors attempted co-culturing the transduced cells with E16 cortical neurons and showed that Pax6 transduced astrocytes might have incomplete assembling of the presynaptic compartment [13]. The presynaptic incompetence of those Ngn2 transduced neurons was later solved by the same group [14] by simply changing the original long terminal repeat driven Moloney Murine Leukemia Virus retroviral vector into a self-inactivating retroviral vector driving gene expression by a stronger chicken beta-actin promoter which has a persistent expression in adult mouse brain. This early work demonstrated already that absolute levels and the dynamic expression of reprogramming factors are of critical importance. With Ngn2 and Dlx2 in the new retroviral construct, the authors could demonstrate that forced expression of those two transcription factors individually in