Fig. 7. Tentative model for the role of Notch in the generation of neurons/glia from neural stem cells in neurospheres. An initial EGF-responsive neural stem cell (NSC1) asymmetrically divides, giving rise to a second stem cell (NSC2) and a progenitor (P1) that appears as inevitably fated to a neuronal identity. As a neuronal precursor, this cell is endowed with a limited proliferation capacity and is responsible for the few neurons generated under all circumstances. The asymmetrical division of NSC2 generates a second precursor (P2). The activation of Notch by P1-produced Dll1 prevents P2 from adopting a neuronal fate. Instead, P2 becomes irreversibly committed to a glial fate. The model postulates that P2 has the potential to acquire either the astrocytic or the oligodendroglial identity through a mechanism independent of Notch signaling. In a second step, Notch would affect the differentiation decision of the precursors already committed to a neuronal or a glial lineage. It would inhibit the differentiation of neurons and oligodendrocytes, while promoting the differentiation of astrocytes.

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